3rd International Symposiumfor Medicinal Sciences

CONTENTS
1

Welcome Message 22

Notice for the Presenters and Attendants to the 3rd International Symposium for Medicinal Sciences 3

3Programs at a Glance 

6

4

Access and Venue Map 

125Program of 3rd International Symposium for Medicinal Sciences 18

6Abstracts 

24Appendix
Abstracts Presented by English in 137th Annual Meeting of the Pharmaceutical Society of Japan
1. Programs 50

2. Abstracts 

63

–1–

1

Welcome Message

It is my great pleasure to hold the 3rd International Symposium for Medicinal Sciences in the 137th Annual Meetingof Pharmaceutical Society of Japan. The objectives of this symposium are to encourage pharmaceutical company
researchers who are interested in drug discovery, to participate in this annual meeting, and also to create an importantinternational platform for all those interested in the medicinal sciences. Since this symposium covers the entire drug
discovery field, we welcome participants including pharmacology, pharmacokinetics, and regulatory sciences.
The one of the feature of this symposium is an invited poster presentations. Since high-caliber presentations from theJapanese and foreign pharmaceutical industries, venture companies, and academia will line up in this presentation,
domestic young researchers who interested in the drug discovery, will have a good chance to discuss with the firstclass researchers for drug discovery around the world.
Chairman of the 3rd International Symposium for Medicinal Sciences
Professor Akira OTAKA(Institute of Biomedical Sciences and Graduate School of
Pharmaceutical Sciences, Tokushima University)

Notice to the Foreign ParticipantsThis Abstract is contained all programs which will be presented by English in 137th Annual Meeting of thePharmaceutical Society of Japan other than 3rd International Symposium for Medicinal Sciences, as an appendix.
The appendix was involved the list of the programs and abstracts presented in English, including Special lectures,
Symposia, and general oral and poster presentations.

–2–Notice for the Presenters and Attendants to the 3rd International

2 Symposium for Medicinal Sciences
1) Registration

The program & abstract book, conference ID/registration certificate will be handed at the registration desk, locatedon the foyer, 2nd floor of Exhibition Building, Sendai International Center.
Registration Desk for Overseas participants will open during the meeting.
Registration Fee
Delegate:

JPY 15,000

Student:

JPY 5,000

Undergraduate student:* Free*U ndergraduate students will be required to present their student ID or student certificate letter at theRegistration Desk onsite.
Registration Fee includes
Admission to all scientific sessions
Admission to exhibition and posters
Meeting program & abstract book
BanquetDate and Time:

18:30, Sunday, March 26

Venue:

Room “Sendai” (4th floor), Hotel Metropolitan Sendai

Fee:

JPY 15,000

Banquet tickets can be purchased at the registration desk.

2) General Information[Name badge]	Upon registration all participants will receive a name badge, which must be worn visibly for the entire durationof the meeting. Your name badge acts as your entrance ticket for the meeting.
[Message board]	A message board will be placed near the registration desk. Participants can exchange messages through theboard.
[Camera, Mobile Phone and Video Recording Policies]
Attendees may not take photos or video of speakers presenting or their slides.

3) Area Map and Venue
See page 12-17–3–4) Guideline for Plenary Lectures– Plenary lecturers have 60 minutes (including Q&A).
– The session room only supports digital presentations using only one LCD projector.
– Please bring your power point file in a USB memory or PC to the speakers’ desk before your session, anddownload/check your presentation data.
– The speakers’ desk will be placed in the foyer, 2nd floor of Conference Building.
– A Windows PC (with Windows 7, PowerPoint 2007, 2010, 2013, 2016) is available. If you are a Macintosh user
or wish to use moving images, please bring your own PC. Please make sure to bring an AC adapter, when you
bring your PC.
– Your PC will be connected to the projector with a “15-pin, mini D-sub” cable. Some PCs (Macintosh or thinlaptops) will require a conversion adapter.
– Please turn off the screen saver, power save mode.
– Set the resolution to XGA (1,024×768).
– After you finish your presentation, please receive your PC immediately inside the room.
– The organization committee will be responsible for deleting all copied data.

5) Guidelines for Poster Presentations< Short Oral Presentation >– You will be asked to make a short presentation (strictly 2 minutes).
Session Room: Room B “Tachibana Conference Hall”, 2nd floor of Conference Building
Presentation Time: 14:20-16:00– Please bring your power point file in a USB memory to the speakers’ desk until 13:00 on the day of yourpresentation, and make sure to check the presentation data. A Windows PC (with Windows 7, PowerPoint 2007,2010, 2013, 2016) is only available.
– The speakers’ desk will be placed in the foyer, 2nd floor of Conference Building.
< Poster Presentation >– Poster session room is located in Room G “Meeting Room 4” and the foyer, 2nd floor of Conference Building.
Abstracts scheduled for presentation in poster session will appear in the Symposium Program. Please refer to thetable below for setup, tear down, and presentation times for posters:

Set-Up8:30-9:00
11:45-13:15

Discussion Time

16:00-17:40
Odd Number: 16:00-16:50
Even Number: 16:50-17:40

Tear Down

17:40-18:00–4–

– Each poster board is labeled with a number and check your poster number.
The poster board surface area is 2.1 m high by 1.2 m wide. Each poster should indicate the title ofpresentation, name of authors and affiliations. Text should be printed in a font large enough to be read
comfortably from a distance of 4-5 feet (1.5m).

"recommended usable area"“160×110cm”– Posters should be displayed on the boards using pushpins that will be available at the Poster Session room. No
other adhesive method is permitted on the boards.

–5–

3 Programs at a Glance

24 March (Fri) 25 March (Sat)
Sendai International Center

Sendai International Center

Conference Bldg

Conference Bldg
Room A

Room A

Room B

2F
Main Hall

Main Hall

8:45

8:45

9:00

9:00

9:15

9:15

9:30

9:30

TachibanaRoom D

9:45

9:45

10:00

10:00

10:15

10:15
10:30

Award Lectures

AL-1

Hagi

Room F

Room H

Room I
1F

Shirakashi 1 Shirakashi 2 Meeting Room 8 Meeting Room 1 Meeting Room 2

Room PA

Room PB

Room J

Room K

2F

1F

SakuraExhibition Hall Meeting Room 1 Meeting Room 2

Symposium

Symposium

Symposium

Let’s challenge New approaches
practicalof exploratory
evidencestudy forbased medicine preventive andeducational
therapeutic
program fortargets inpharmacy
neurodegenerative
Award Lectures students andand psychiatricpharmacists
disorders

How do we
promoteresearch
integrity?

Risk
assessment andmanagement ofa small amountof carcinogens
possibly
exposed in ourordinary life

S01

PL

Naoto OKU

Room E
3F

Symposium

Plenary Lecture

10:30

Room C

2F

Exhibition Bldg

S02

S03

AL-10

Oral
Presentations

Oral
Presentations

Oral
Presentations

25F-am01～
25F-am13

25H-am01～
25H-am13

25I-am01～
25I-am13

Toshihide
TAKEUCHI

PosterPresentations

PosterPresentations

25PA-am001～
25PA-am140

25PB-am001～
25PB-am228

S04【Discussion】 【Discussion】
Odd No.
Odd No.
9:45~10:45
9:45~10:45
Even No.
Even No.
10:45~11:45
10:45~11:45

10:45

10:45

11:00

11:00

11:15

11:15

11:30

11:30

11:45

11:45

12:00

12:00

12:15

12:15

Luncheon Seminar

Luncheon Seminar Luncheon Seminar

Luncheon Seminar

Luncheon Seminar Luncheon Seminar

12:30

12:30
12:45

CRECON
Chugai
MEDICAL
Pharmaceutical
ASSESSMENT
Co., LTD.
INC.

Agilent
Technologies
Japan, Ltd.

Kyowa Chemical
Industry Co., Ltd.

12:45

Japan EMF
Information
CenterOno
PharmaceuticalCo., Ltd. /AstraZeneca K. K.

13:00

13:00

13:15

13:15

13:30

13:30

Symposium

Symposium

13:45

GeneralAssembly

Takeo
KAWABATAAward Lectures

AL-11

HirotoHATAKEYAMA
11:36

LS01

AL-2

Hiroki
SHIGEHISA

Kazuki SAITO

14:15

14:15

14:30

14:30

14:45

14:45

15:00

15:00

15:15

15:15

15:30

15:30

15:45

15:45

16:00

16:00

Award Lectures

AL-13

Taniyuki
FURUYAMA

14:40

Special Lectures

SL-1

Hiro-oHAMAGUCHI

Symposium

S08

16:15

AL-3

Hideo SAJI

16:30

16:45

16:45

17:00

17:00

17:15

17:15

17:30

17:30

17:45

17:45

18:00

18:00

LS05

GS01

Award Lectures

AL-5

MasaakiKURIHARAAward Lectures
Award Lectures

16:30

Symposium

S09

Effective
State-of-theThe front
communication art technology
line and new
betweenby young
progress inpharmacists
neuroscientists cardiovascularand foreign
researchpatients at-Searching for
medical teambreakthroughin treatments ofcardiovasculardisease-Symposium

16:15

Symposium

LS04

LS06

AL-12

13:45
14:00

LS03

11:36

Award Lectures
Award Lectures

14:00

LS02

11:36

AL-6

S15

Symposium

S16

S10

Oral
Presentations

Oral
Presentations

Oral
Presentations

25F-pm01～
25F-pm17

25H-pm01～
25H-pm17

25I-pm01～
25I-pm17

Symposium

GS02

Challenges
Fascination
The challenge
Hidetoshi
to improveof sacran, aof young
ARAKAWAthe prdiction
polysaccharide
researchers
accuacy of the from Aphanotheceleading the
16:35
non-clinical tests
sacrumfuture and16:39
for human CNS
development
adverse effects:of thePotentials
pharmaceutical
16:50
of artificial
research on
intelligenceandcancerAward Lectures
human ESC/iPSC-derived
Takashineurons
SUZUKI

AL-7

17:40

E : English Presentation–6–

PosterPresentations

PosterPresentations

25PA-pm001～
25PA-pm132

25PB-pm001～
25PB-pm307【Discussion】 【Discussion】
Odd No.
Odd No.
14:15~15:15
14:15~15:15
Even No.
Even No.
15:15~16:15
15:15~16:15

Problem-SolvingPartnership
Type Program for for NTDs drug
the Development
discoveryof Highlyoriginated in
Skilled Human
Japan
Resources(- Project for
Nurturing
Pharmacists who
Provide TeamBased Community
Healthcare -)Symposium

Symposium

Current statusof reverse
translational
research
conducted
by hospital
pharmacists

How can the
researchers inuniversity beinvolved withthe streamof hospital
preparations
from themedical needs
to the clinicalapplication?

S17

16:39

16:39

S11

S18

Tohoku University Kawauchi-Kita Campus

Sendai International Center

TohokuUniversity
Multimedia Education andExhibition Bldg Centennial Hall Research Complex

Lecture Rooms C

Room L

Room M

Room N

Room O

1F

2F

2F

2F

Meeting Room 3 Kawauchi Hagi Hall Multimedia Research Hall Lecture room

Room P

Room Q

Room R

Room S

Room T

Room U

1F
C101

C102

Room V

Room W

Room X

2F
C105

C106

C201

C202

Room Y
3F

C205

C206

C301

C302

8:45
9:00
9:15

Symposium

Symposium

Symposium

Utilizing soft
molecularsystems for
drug discovery
research ~theconcerteduse of theory,
measurements
and functional
design~Research
strategies
for the postgolden-age
GPCR drug
discovery

Role of pharmacy
in the promotionof drug safety inpharmacotherapy

S05

S06

S07

9:30
9:45
Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

10:00

25P-am01～
25P-am13

25Q-am01～
25Q-am13

25R-am01～
25R-am13

25S-am01～
25S-am13

25T-am01～
25T-am13

25U-am01～
25U-am13

25V-am01～
25V-am13

25W-am01～
25W-am10

25X-am01～
25X-am13

25Y-am01～
25Y-am13

10:15
10:30
10:45
11:00
11:15

11:36

11:36

11:36

11:36

11:36

11:36

11:36

11:36

11:36

11:30
11:45

Award Lectures

AL-20

12:00

Naomi KURATA

Luncheon Seminar

12:15

SEED Co., Ltd.

12:30

LS07

12:45
13:00
13:15
13:30
Symposium

S12

Structural
biology of lipidbinding proteins-Recent
developments-

Symposium

S13

Young
innovators
driving the next
generation ofacademic drug
discovery

Symposium

S14

13:45

New Trendsof Natural
Products
Chemistry ―Redesign of
Biosynthesis

14:00
14:15
14:30
Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

25P-pm01～
25P-pm16

25Q-pm01～
25Q-pm17

25R-pm01～
25R-pm17

25S-pm01～
25S-pm16

25T-pm01～
25T-pm16

25U-pm01～
25U-pm17

25V-pm01～
25V-pm17

25W-pm01～
25W-pm15

25X-pm01～
25X-pm17

25Y-pm01～
25Y-pm17

14:45
15:00
15:15
15:30
15:45

Symposium

Symposium

Symposium

Scientific basisof plasmaand mechanobiology indiseasetherapy anddrug delivery
towards clinicalapplications

Young
Challengers
in Synthetic
Organic
Chemistry:
DeeperUnderstanding
and Recent
Advancement
in Synthetic
Organic
Chemistry

Modifiednucleic acids
and regulation 16:27
of diseases

S19

S20

S21

16:00

16:03

16:15
16:27

16:27

16:30
16:39

16:39

16:39

16:39

16:39

16:39

16:45
17:00
17:15
17:30
17:45
18:00

–7–

26 March (Sun)Sendai International Center
Conference Bldg
Room A

Room B

Room CRoom D

2F
Main Hall

Room E

Room F

Exhibition Bldg
Room H

3F

Tachibana

Hagi

Room I

Room G

1F

Room PA

Room PB

Room J

Room K

2F

Shirakashi 1 Shirakashi 2 Meeting Room 8 Meeting Room 1 Meeting Room 2 Meeting Room 4

Room L

1F
SakuraExhibition Hall Meeting Room 1 Meeting Room 2 Meeting Room 3

8:45
9:00

E

9:15
Special Lectures
9:30

SL-2

Eric KOOLAward Lectures

AL-18

Tomokazu
YOSHINAGA
9:40

Award Lectures

10:00

AL-19
Nobuhiro
OIKAWA

10:15

10:25

SL-3

Takuzo AIDA

11:00
11:15

12:15

10:40

AL-15

Kazuya NAGANO
10:10

Symposium

Symposium

Symposium

Recentadvancesin clinicalchemistry fordeveloping
novel drug
treatment
strategies

Frontier oftranslational
researchby young
investigators
aim to innovative
drug discovery
and drug
fostering

Creation ofComplex
Functional
Molecules
by Rational
Redesign of
Biosynthetic
Machineries

Appropriate
The structuralplanning andstudies ofmanagement
membraneof annual
proteins bymeeting forleading edge
all attendees;
technologies:
application of their forthcoming
active learning contribution topharmacology
and drugdevelopment

S22

GS03

OS23

Oral
Presentations

Oral
Presentations

Oral
Presentations

26F-am01～
26F-am13

26H-am01～
26H-am13

26I-am01～
26I-am13

PosterPresentations

PosterPresentations

26PA-am001～
26PA-am140

26PB-am001～
26PB-am335【Discussion】 【Discussion】
Odd No.
Odd No.
9:45~10:45
9:45~10:45
Even No.
Even No.
10:45~11:45
10:45~11:45

AL-16

Hideyuki KONISHI

E 10:50

International
Symposium
for Medicinal Award Lectures
Sciences

ISMSPL01

11:30

12:00

Award Lectures

SymposiumAward Lectures
Special Lectures

11:45

Toru
KOMATSU

10:20

10:30
10:45

AL-14

9:40

9:45

E

Award Lectures

S24

Symposium

S25

AL-17

Jun
SHIMOKAWA
11:36

Ross D. KING

11:36

11:36

Award Lectures

AL-4

ShigekiSASAKI

Luncheon Seminar Luncheon Seminar Luncheon Seminar Luncheon Seminar

LS08

LS09

Luncheon Seminar Luncheon Seminar Luncheon Seminar

Thermo Fisher
Scientific

Sawai
Daiichi Sankyo
OtsukaPharmaceutical
Company /PharmaceuticalCo., Ltd.
MitsubishiCo., Ltd.
Tanabe Pharma
Corporation

LS12

LS13

LS14

Symposium

Symposium

Symposium

Symposium

Symposium

PSJ'sorganizational
SriramSUBRAMANIAM approach to thepromotion ofgender equality
14:20

Approachto the Next
Remedy by
Multidiscipline
Researchers-for Responding
to Unmet
Medical Needs-

New
The mechanisms Cutting edge
development of of epileptogenesis of retinal circuit
the risk benefit and the effective
research
communicationintervention
PosterPoster- For safety
strategies in
Presentations Presentations
information to bepediatric andcommunicatedelderly patients
26PA-pm001
26PB-pm001
and understood～～
sufficiently26PA-pm133
26PB-pm312

SCIEX

12:30

Shimadzu
Corporation

LS10

Astellas
Pharma Inc.

LS11

12:45
13:00
13:15
13:30
13:45
14:00

E

International
Symposium
Special Lectures for Medicinal
Sciences
SL-4
Masayuki
YAMAMOTO

14:15

15:00
15:15

E
Special Lectures

SL-5

Ruedi
AEBERSOLD

International
Symposium
for Medicinal
Sciences
ISMS:

E

Poster Short
Presentation

15:30

S29

Oral
Presentations

Oral
Presentations

Oral
Presentations

26F-pm01～
26F-pm17

26H-pm01～
26H-pm17

26I-pm01～
26I-pm17

OS33

Yaichiro
KOTAKE

E 16:10Special Lectures

SL-6

International
educational
trends forpharmaceuticalresearchers in thenext generation

Symposium

S34

16:27

Christina WHITE

16:45
17:00

S31

【Discussion】 【Discussion】
Odd No.
Odd No.
14:15~15:15
14:15~15:15
Even No.
Even No.
15:15~16:15
15:15~16:15

Symposium

AL-8

E

16:00

16:30

S30

Award Lectures FIP forum 2017:

15:45

16:15

GS04

E

14:30
14:45

ISMSPL02

OS28

International
Symposium
for Medicinal
Sciences
16:50
ISMS:
Award Lectures
PosterPresentation

16:39

16:39

International
Symposium
for Medicinal
Sciences
ISMS:
PosterPresentation

AL-9

Mitsuhiro
ARISAWA

17:15
17:30
17:40

17:40

17:45
18:00

E : English Presentation–8–

Symposium

S35

Symposium

S36

Protectioun
Progress of
For promotionof Skin fromhealth careof theDryness andinformation
participation of
UV Radiation
technologies the pharmacist-Approach from- On-site
to homeCosmeticsinflection of the medical care
new information
technologies -Tohoku University Kawauchi-Kita Campus

TohokuUniversity
Centennial Hall Multimedia Education andResearch Complex

Sendai Civic
Auditorium

Lecture Rooms C

Room M

Room N

Room O

2F

2F

2F

Kawauchi Hagi Hall Multimedia Research Hall Lecture room

Room P

Room Q

Room R

Room S

Room T

Room U

1F
C101

C102

Room V

Room W

Room X

2F
C105

C106

C201

C202

Room Y

Room Z

3F
C205

C206

C301

C302

8:45
9:00

E
Special Lectures Symposium

SL-7Alexander
MAKAROV

S26

9:15
Symposium

S27

Currents state
The efforts byand future
pharmacists toprospects of implement home
doctoral course medical care forfor students
heart failure - a
graduatedcomprehensivefrom division of
integrated
pharmacy (4- community care year program)- A survey
Special Lecturescommissioned
to PSJ from theHidenoriMEXTICHIJO

9:30
9:45
Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

10:00

26P-am01～
26P-am13

26Q-am01～
26Q-am13

26R-am01～
26R-am13

26S-am01～
26S-am13

26T-am01～
26T-am13

26U-am01～
26U-am13

26V-am01～
26V-am13

26W-am01～
26W-am12

26X-am01～
26X-am12

26Y-am01～
26Y-am13

10:15
10:30

SL-8

10:45
11:00

11:12

11:15
11:24
11:36

11:36

11:36

11:36

11:36

11:36

11:36

11:30

11:36

11:45
12:00
12:15
12:30
12:45
13:00
13:15
13:30

Special Lectures

Symposium

SL-9

S32

Katsumi
MATSUZAKI

13:45

Forefrontof cancer
targetingtherapy

14:00
14:15
14:30

Special Lectures

SL-10

Keiji
MARUOKA

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

26P-pm01～
26P-pm17

26Q-pm01～
26Q-pm17

26R-pm01～
26R-pm16

26S-pm01～
26S-pm13

26T-pm01～
26T-pm17

26U-pm01～
26U-pm17

26V-pm01～
26V-pm17

26W-pm01～
26W-pm17

26X-pm01～
26X-pm17

26Y-pm01～
26Y-pm11

PublicLecture

14:45
15:00
15:15

15:27

15:30

Symposium

Symposium

Frontiers inimmunology forinnovative drug
development

Frontiers of
Research
on Anti-Viral
Infectious
Diseases16:39
Boundary
between Host
Defense andViral Offense-

S37

15:45

15:51

S38

16:00
16:15
16:27

16:30
16:39

16:39

16:39

16:39

16:39

16:39

16:45
17:00
17:15
17:30

18:30

–9–

Hotel Metropolitan Sendai
Banquet (buffet style)

17:45
18:00

27 March (Mon)
Sendai International Center
Conference Bldg
Room A

Room B

Room CRoom D

Room E

2F
Main Hall

TachibanaRoom F

Exhibition Bldg
Room H

3F
Hagi

Room I
1F

Shirakashi 1 Shirakashi 2 Meeting Room 8 Meeting Room 1 Meeting Room 2

Room PA

Room PB

Room J

Room K

Room L

2F

1F

SakuraExhibition Hall Meeting Room 1 Meeting Room 2 Meeting Room 3

8:45
9:00

E

9:15
Symposium

Symposium

Symposium

Symposium

Recent advances in
DDS research on the
key molecule "cellpenetrating peptides"that controls the
kinetics of the nextgeneration drug target"biopharmaceuticals"

Catalysis
Bridging
Material
Science andLife Science

Lifestyleinspires future
pharmacotherapy
and drug
discovery

PSJ-PSK Joint
RecentVarious
PosterPosterSymposium:
advances inphysiological
Presentations
Presentations The mechanism, the networking
actions
evaluation,and crosstalk
mediated
27PA-am001
27PB-am001
prediction andthroughthrough a Na+/～～
diagnosis ofseveral organs
glucose co27PA-am141
27PB-am255
drug-induced
to affect thetransporter
liver injury
homeostasis of (SGLT) and theliving organism possibility of the【Discussion】 【Discussion】
innovative drug
Odd No.
Odd No.
development
9:45~10:45
9:45~10:45
Even No.
Even No.
10:45~11:45
10:45~11:45

S39

9:30
9:45
10:00
10:15

S40

S41

10:30
10:45

OS42

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

27E-am01～
27E-am09

27F-am01～
27F-am13

27H-am01～
27H-am13

27I-am01～
27I-am13

10:48

11:00

Symposium

S43

Symposium

S44

11:15
11:30

11:36

11:36

11:36

11:45
12:00
Luncheon Seminar

LS15

12:15

Live Cell SuperResolution Imaging
Research TeamRIKEN Center
for Advanced
Photonics

12:30
12:45
13:00
13:15
13:30
13:45

Nobel Lecture
Broadcasting(Live)

Symposium

S47

Symposium

S48

Symposium

Symposium of Frontier of theMetallomic
The Division
middle size
research basedof Physicaldrug discovery- on determining
Sciences of the
Middlethe relationshipPharmaceuticalmolecular
between biometals
Society ofstrategy:
and biologicalJapan
Creationreactions: Fromof higher
investigation of
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molecules
role of biometals
by integrated
to establishment
synthesisof novel
pharmacotherapy
for major diseases

14:00
14:15
14:30
14:45
15:00
15:15

Symposium

S49

S51

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

27E-pm01～
27E-pm1427F-pm01～
27F-pm17

27H-pm02～
27H-pm17

27I-pm01～
27I-pm17

15:30

PosterPresentations

PosterPresentations

27PA-pm001～
27PA-pm136

27PB-pm001～
27PB-pm191

Symposium

S52

Evaluation
Platformand guarantee developmentof quality offor drug
pharmaceutical
discovery
education by
utilizing
the Japan
silkworm
Accreditation towards "Novel
Board forIndustrial
Pharmaceutical
Revolution"
Education【Discussion】 【Discussion】
Odd No.
Odd No.
14:15~15:15
14:15~15:15
Even No.
Even No.
15:15~16:15
15:15~16:15

15:45
16:00

Nobel Lecture
Broadcasting(recorded)

16:15
16:30
16:45
17:00

Symposium

S55

Chemical
Biology for
Pharmaceutical
Sciences(Developmentof practicalchemicalbiotechnology)

Symposium

S56

Frontier ofSynthetic
Organic
Chemistry
Opened by
Precisely
Designed
Catalysts with
Specified Field

Symposium

Symposium

Symposium

Iron Ion as a
New Target for
Drug Discovery

Current trends
in analyticaltechnologies
which promote thedevelopment ofbiopharmaceuticals

An explosion ofphotoswichable
molecules for
spatiotemporalvisualizationand control ofbiological activity

S57

16:03
16:15

16:39

16:39

17:15
17:30
17:45
18:00

E : English Presentation– 10 –S58

S59

Tohoku University Kawauchi-Kita Campus

TohokuUniversity
Centennial Hall Multimedia Education andResearch Complex

Lecture Rooms C

Room M

Room N

Room O

2F

2F

2F

Kawauchi Hagi Hall Multimedia Research Hall Lecture room

Room P

Room Q

Room R

Room S

Room T

Room U

1F
C101

C102

Room V

Room W

Room X

2F
C105

C106

C201

C202

Room Y
3F

C205

C206

C301

C302

8:45
9:00
9:15

Symposium

Symposium

Symposium

Novel
Developmentof Toxicology
Studies ofChemicals

Pharmaceutical
Compounds inthe Environment-Distribution,
Ecological effects,
and Purification
Technologies-

Knowledgeof druginteractions
to takeadvantage inthe pharmacist

S45

S46

S50

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

27P-am01～
27P-am13

27Q-am01～
27Q-am12

27R-am01～
27R-am12

27S-am01～
27S-am12

27T-am01～
27T-am13

27U-am01～
27U-am13

27V-am01～
27V-am13

27W-am01～
27W-am13

27X-am01～
27X-am13

9:30
9:45
10:00
10:15
10:30
10:45
11:00
11:15

11:24

11:24

11:24

11:36

11:36

11:36

11:36

11:36

11:36

11:30
11:45
12:00
12:15
12:30
12:45
13:00
13:15

Nobel
LectureSymposium

Yoshinori
OHSUMI

Frontier
Frontier of
Pharmaceutics tobiomedical
Be Explored byscience by
Young Scientists:biomolecule
Opening Up
analysis based
New Horizon of
on mass
Pharmaceutics for spectrometry
Next Generation
Innovative Drug
Discovery andDevelopment using
Nanoscience andNanotechnology

NL

S53

Oral
Presentations

Symposium

S54

Oral
Presentations
27X-pm01～
27X-pm06

27U-pm01～
27U-pm04

13:30
13:45
14:00

14:03

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations

Oral
Presentations 14:27

14:15

27P-pm01～
27P-pm09

27Q-pm01～
27Q-pm12

27R-pm01～
27R-pm16

27S-pm01～
27S-pm17

27T-pm01～
27T-pm17

27V-pm01～
27V-pm17

27W-pm01～
27W-pm14

14:30
14:45
15:00

15:03

15:15
15:30
15:39

15:45
Nobel Lecture
Broadcasting(recorded)

16:03

16:00
16:15

16:27

16:30
16:39

16:39

16:39

16:45
17:00
17:15
17:30
17:45
18:00

– 11 –

4 Access and Venue Map

Access◆Map

Tohoku Univ.

Kawauchi-Kita Campus

Tohoku Univ. Centennial Hall:

Kawauchi Hagi Hall

Hotel Metropolitan Sendai(Banquet on March 26)

Sendai International Center◆Access
Sendai Airport

By AirSendai Airport Access Line:
17min. - 25min. [650 yen]

ＪＲ Sendai Station（West Entrance）

By Train
TAXI:
12min. [1,200 yen]

Subway Tozai - Line:
6min. [200 yen]

Subway Tozai - Line:

Subway Tozai - Line:

Kawauchi Station
on foot 3min.

Tohoku Univ.

International Center Station

on foot 10min.

Kawauchi-Kita Campus

Subway Tozai - Line:
5min. [200 yen]

TAXI:
10min. [1,000 yen]

on foot 10min.

Tohoku Univ. Centennial Hall:

Kawauchi Hagi Hallon foot 7min.

on foot 3min.

Sendai International Centeron foot 10min.
on foot 15min.

– 12 –

Area Map
The Miyagi Museum of Art
Convenience Store

Tohoku Univ.

Multimedia Research Hall
SubwayKawauchi Station

Tohoku Univ.

Lecture Rooms C

SubwayInternational
CenterStationTohoku Univ. Centennial Hall:

Kawauchi Hagi Hall

Sendai International Center
Tohoku Univ.
Main LibraryP

Conference Bldg.

Ougi-zaka(80-step)

Sendai International Center

Exhibition Bldg.

050

Sendai City Museum

100m

Aoba Castle Facility

Room(Under Construction)

Place

A, B, C, D, E, F, G, H, I, PA

Sendai International Center Conference Bldg.

J, K, L, PB

Sendai International Center Exhibition Bldg.

M

Kawauchi Hagi Hall

N

Kawauchi-Kita Campus: Multimedia Research Hall

O, P, Q, R, S, T, U, V, W, X, Y

Kawauchi-Kita Campus: Kawauchi Lecture Rooms C

Exhibition
Exhibition Room

Place
Sendai International Center Exhibition Bldg. Exhibition Hall 2

Registration
Registration & Information Desk

Place
Sendai International Center Exhibition Bldg. Foyer
Kawauchi-Kita Campus: Kawauchi Lecture Rooms C １F C103
Sendai International Center Conference Bldg. 2F Lobby

PC Center

Kawauchi-Kita Campus: Kawauchi Lecture Rooms C ２F C203
BanquetHotel Metropolitan Sendai 4F「千代（Sendai）」– 13 –

Sendai International Center
Conference Bldg. 1F

EV

Cloak②

Room: H

【Meeting Room 1】

Room: I

【Meeting Room 2】

Reception

EV【Cafe "Leaf"】

Entrance

Conference Bldg. 2F

Room: A

【Main Hall】

Room: PA
【Sakura】

PC Center

2F Lobby

Room: C
【Hagi】

Secretariat【Meeting Room 5】

Room: B【Tachibana】

to Exhibition Bldg.

Room: G

【Meeting Room 4】– 14 –

EV

Conference Bldg. 3F

Room: F

【Meeting Room 8】

Room: D

【Shirakashi 1】

Room: E

【Shirakashi 2】
EV

Exhibition Bldg.
to Conference Bldg. 1FRegistration & Information Desk
Room: L

【Meeting Room 3】

to Conference Bldg. 2F

Lunchtime Seminars Ticket Counter

Exhibition Seminar【Meeting Room 4】

from Subway
International
Center Station

Foyer

Room: K

【Meeting Room 2】

Poster Room Information

Room: J

【Meeting Room 1】

Room: PB

【Exhibition Hall 1】

Cloak①– 15 –

Exhibition Room
【Exhibition Hall 2】

Tohoku University Centennial Hall Kawauchi Hagi Hall

1F

バーコーナーEV

PC Center【1F Lobby】

Entrance

2F
EV

PC Center

Room: M

【Hagi Hall】

Foyer– 16 –

Tohoku University Kawauchi-Kita Campus
Multimedia Education and Research Complex 2F

EV

Room: N【Multimedia Research Hall】【M206】

PC Center
Multimedia Education and Research Complex 1F

EV

Lecture Rooms C 1F

Room: S

Room: R

Cloak③

Room: P

Room: Q

【C103】【C106】【C101】

Lecture Rooms C 2F

【C105】【C102】【C104】

Registration &Information Desk

Room: W

Room: V

C204

Room: T

Room: UPC Center

Room: X

Room: Y【C206】【C205】

Room: O

【Lecture room】【C201】【C202】

Lecture Rooms C 3F

【C301】– 17 –【C302】【C203】

5

Program of 3rd International Symposium for Medicinal Sciences

Sunday, 26 March 10:40 ～ 11:45 / 13:15 ～ 17:40
Plenary Lecture: Room B Tachibana Conference Hall, Sendai International Center (Conference building 2F)

Invited Poster Presentation: Room G Meeting Room 4, Sendai International Center (Conference building 2F)

3rd International Symposium for Medicinal Sciences
10:40 ～ 10:45
Opening Remark 

Chairman: Akira OTAKA（Tokushima University）

10:45 ～ 11:45
Plenary Lecture 1 ISMS-PL01

Chairman: Tsuneaki SAKATA（Shionogi & Co., Ltd.）

Robot Scientists: Automating Drug Design

Ross D. KING（University of Manchester）

13:15 ～ 14:15
Plenary Lecture 2 ISMS-PL02

Chairman: Tatsuhiko KODAMA（The University of Tokyo）

Recent Advances in cryo-EM: Applications to Drug Discovery
Sriram SUBRAMANIAM（National Cancer Institute, NIH）

14:20 ～ 17:40
Invited Poster Presentation
14:20 ～ 16:00

Short Presentation for Invited Poster Presentation

16:00 ～ 17:40

Poster Presentation
Discussion   Odd Number: 16:00 ～ 16:50
Even Number: 16:50 ～ 17:40

26G-ISMS01 Unstructured Protein : A New Approach for Drug Discovery○ Takenao ODAGAMI1, Yoichiro HIROSE1, Yoshimasa IMAMURA1, Akira KATOH1,
Tadashi MISHINA1, Hiroyuki KOUJI1（1Research & Development, PRISM BioLab Co., Ltd.）
26G-ISMS02 Development of Macrocyclic Peptide Targeting Ebola Glycoprotein○ Shiori UMEMOTO1, Junki MARUYAMA2, Ayato TAKADA2, Hiroaki SUGA1（1Department
2of Chemistry, Graduate School of Science, The University of Tokyo, Department of Global Epidemiology, ResearchCenter for Zoonosis Control, Hokkaido University）

26G-ISMS03 Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide
Destruxin B as a Negative Regulator for Osteoclast Morphology○ Hiroshi SATO1,2, Masahito YOSHIDA1, Hayato MURASE3, Hiroshi NAKAGAWA3,
Takayuki DOI1（1Graduate School of Pharmaceutical Sciences, Tohoku University, 2Mitsubishi Tanabe Pharma
Corporation,3

Department of Applied Biological Chemistry, Chubu University）

26G-ISMS04 SAR Exploration of Selective Kinase Inhibitors based on the “Head-to-Tail” Approach:Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds○ Satoru NOJI1, Noriyoshi SEKI1, Takaki MAEBA1, Takayuki SAKAI1, Eiichi WATANABE1,
Katsuya MAEDA1, Kyoko FUKUSHIMA1, Toru NOGUCHI1, Kazuya OGAWA1,
Yukiyo TOYONAGA1, Tamotsu NEGORO1, Hisashi KAWASAKI1, Makoto SHIOZAKI1
1（ Central Pharmaceutical Research Institute, Japan Tobacco Inc.）– 18 –

26G-ISMS05 Search for Anti-leukemic Drugs Targeting the Transcription Factor Runx1 by INTENDD○ Masaaki SHIINA1, Shiho BABA1, Akiko UCHIYAMA1, Chikako OKADA1,
Takeshi TANAKA2, Ken IKEDA2, Shigetsugu KAWAKITA2, Takao MATSUZAKI2,
Hirotsugu KOMATSU2, Masato HOSODA2, Kazuhiro OGATA1（1Yokohama City University,
2

Graduate School of Medicine, Interprotein Corporation）

26G-ISMS06 Evaluation of Novel Anti-Dengue Candidates Using In Silico and In Vitro Approaches○ Yu-Shi TIAN1, Hitoshi MATSUDA2, Xinzhe LIU2, Norihito KAWASHITA2,3,
Tatsuya TAKAGI2,3（1Graduate School of Information Science and Technology, Osaka University, 2Graduate
3

School of Pharmaceutical Sciences, Osaka University, Graduate School of Information Science and Technology,
Osaka University Research Institute for Microbial Diseases）

26G-ISMS07 Development and Construction of an Original Compound Library for CNS Drug
Discovery: Combining Computational and Wet Data to Enhance CNS Drug-likeness○ Daiju HASEGAWA1（1Medicinal Chemistry, Neurology Tsukuba Research Department, Discovery, Medicine
Creation, Neurology Business Group, Eisai Co., Lid.）

26G-ISMS08 Structure-based Design, Synthesis, and Biological Evaluation of Imidazo[1,2-b ]Pyridazine- based p38 MAP Kinase Inhibitors○ Akira KAIEDA1, Masashi TAKAHASHI1, Takafumi TAKAI1, Masayuki GOTO1,
Takahiro MIYAZAKI1, Yuri HORI1, Satoko UNNO1, Tomohiro KAWAMOTO1,
Toshimasa TANAKA1, Sachiko ITONO1, Terufumi TAKAGI1, Teruki HAMADA1,
Mikio SHIRASAKI1, Kengo OKADA1, Gyorgy SNELL2, Ken BRAGSTAD2, Bi-Ching SANG2,
Osamu UCHIKAWA1, Seiji MIWATASHI1（1Takeda Pharmaceutical Company Limited, 2Takeda
California, Inc.）

26G-ISMS09 Flow Chemistry: New Horizons in Chemical Space for the Creation of Next Generation
Libraries
Daniel BLANCO-ANIA3, Sagar Ashok GAWADE1, Luuk MAARTENSE1,
Roel VERLEIJSDONK1, Remco MERKX2, Huib OVAA2, Floris RUTJES1, Marjon BOLSTER3,
Luc ZWINKELS3, Joeri SCHEIDT3, Pauline van MEURS3, Jorg BENNINGSHOF3,○ Norimasa MORITA3（1Radboud University, 2Leiden UMC (Former NKI), 3Mercachem）
26G-ISMS10 Transition Metal-Free, Tryptophan-Selective Bioconjugation of Proteins○ Kounosuke OISAKI1, Yohei SEKI1, Takashi ISHIYAMA1, Daisuke SASAKI1,2, Junpei ABE1,
Yohei SOHMA1,2, Motomu KANAI1,2（1Graduate School of Pharmaceutical Sciences, The University of
2Tokyo, JST, ERATO Kanai Life Science Catalysis Project）

26G-ISMS11 Total Synthesis of Halichondrin A and C○ Akihiko YAMAMOTO1, Atsushi UEDA1, Paul BRÉMOND1, Paolo S. TISENI1,
Daisuke KATO1, Yoshito KISHI1（1Department of Chemistry and Chemical Biology, Harvard University）
26G-ISMS12 Parallel Fluorescent Probe Synthesis Based on the Large-scale Preparation of BODIPYFL Propionic Acid
○ Taisuke KATOH1, Masato YOSHIKAWA1, Takeshi YAMAMOTO1, Ryosuke ARAI1,
Noriyuki NII1, Yoshihide TOMATA1, Shinkichi SUZUKI1, Ryoukichi KOYAMA1,
Nobuyuki NEGORO1, Takatoshi YOGO1（1Pharmaceutical Research Division, Takeda Pharmaceutical
Company, Ltd）

26G-ISMS13 Improvement in Pharmacokinetics and In Vivo Activity of Somatostatin by Chemical
Glycosylation○ Hirofumi OCHIAI1, Jun IGARASHI1, Hayato SAIJO1, Takahiro YAMAMOTO1,
Yuji NISHIUCHI1, Akio KANATANI1, Taiji SHIMODA1（1GlyTech, Inc.）
26G-ISMS14 Development of an Oxidative Mizoroki-Heck Reaction for Late-stage C-HFunctionalization of Complex Molecules and Application to Pharmaceutical Studies○ Kenji WATANABE1, Amrita DAS1, Takumi KIMIJIMA1, Tomohiro YAMASHITA1,
Kazuhide INOUE1, Makoto TSUDA1, Takashi OHSHIMA1（1Graduate School of Pharmaceutical
Sciences, Kyushu University）– 19 –

26G-ISMS15 Functional Characterization of Acetylcholine Receptors in Human HippocampusDerived Neurons○ Kazuyuki FUKUSHIMA1, Kazuto YAMAZAKI2, Norimasa MIYAMOTO3,
Kohei SAWADA3（1Neurology Tsukuba Research Department, Discovery, Medicine Creation, Neurology
2

3

Business Group, Eisai Co., Ltd., Technology Cross Point Laboratory, hhc Data Creation Center, Eisai Co., Ltd., Global
CV Assessment, BA CFU, Medicine Development Center, Eisai Co., Ltd.）

26G-ISMS16 Analgesic Effect of Novel 11 β -HSD1 Inhibitor ASP3662 and its Mechanism of Action
in a Spinal Nerve Ligation Model of Neuropathic Pain
○ Tetsuo KISO1, Toshihiro SEKIZAWA1, Mina TSUKAMOTO1, Junko YARIMIZU1,
Shuichiro KAKIMOTO1（1Drug Discovery Research, Astellas Pharma Inc.）
26G-ISMS17 Atomic-Scale Investigation on Acetaminophen Crystals with Stable and Metastable
Phases by Frequency Modulation Atomic Force Microscopy in Aqueous Solution○ Naritaka KOBAYASHI1, Kazuki OKANO2, Yoichiro MORI3, Shun FUKUKITA3,
Mihoko MARUYAMA4, Hiroaki ADACHI3,5, Kazufumi TAKANO4,5, Satoshi MURAKAMI5,6,
Hiroyoshi MATSUMURA5,7, Tsuyoshi INOUE3,5, Masashi YOSHIMURA5,8, Yusuke MORI3,5,
Seiichiro NAKABAYASHI1, Hiroshi YOSHIKAWA1,3（1Graduate School of Science and Engineering,
2

3

Saitama University, Faculty of Science, Saitama University, Graduate School of Engineering, Osaka University,
4
5
6
Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, SOSHO, Inc., Graduate School
7of Bioscience and Biotechnology, Tokyo Institute of Technology, College of Life Science, Ritsumeikan University,
8
Institute of Laser Engineering, Osaka University）

26G-ISMS18 Anti-inflammatory Flavan-dihydrochalcones with Unprecedented Carbon Skeletonsfrom Daemonorops Draco○ Ping-Chung KUO1, Hsin-Yi HUNG1, Tsong-Long HWANG2, Tian-Shung WU1（1 School of
Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 
2Graduate Institute of Natural Products, College of Medicine, Chang Gung University）

26G-ISMS19 Development of a Fully Automated HPLC System (ASAPrepTM) Designed for Multiple
Compound Purifications○ Chie KUSHIBE1, Katsuhiko MIWA1, Hidetoshi TERADA2, Yuji KATSUYAMA2（1Medicinal
2

Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Life
Science Business Department, Analytical & Measurement Instruments Division, Shimadzu Corporation）

26G-ISMS20 Discovery of a Novel PDE10A Inhibitor as Highly Effective for Schizophrenia○ Yoichi KADOH1, Takehiko MATSUMURA1, Yoshihito TANAKA1, Mitsuya HONGU1,
Haruko MIYOSHI1, Mayumi KIMURA1, Kei TAKEDOMI1, Kenji OMORI1, Jun KOTERA1,Takashi SASAKI1, Kiichi TANAKA1, Keiko MIWA1, Tamaki KOBAYASHI1,
Hiroyuki TANIGUCHI1, Taketoshi ISHII1, Yumi WATANABE1, Haruna ITODA1,
Rikiya OHASHI1, Kouki KOJIMA1, Masaya FUKUDA1, Saori SATO1, Itsuko NAKAMURA1,
Toshiaki SAKAMOTO1, Toshiyuki HIMIYAMA1, Masataka HIKOTA1, Eiji KAWANISHI1
1（ Mitsubishi Tanabe Pharma Corporation）

26G-ISMS21 Nucleic Acid Drugs Large Scale Manufacturing and Specification Assay– Equivalency
Solid Phase versus AJIPHASE® and Oligonucleotide Sequences Confirmation for IND
and NDA○ Satoshi INOUE1, Hirokazu NANKAI1, Emi SAITO1, Hideaki SATO1, Kazuhiko YUYAMA1
1（ GeneDesign, Inc.）

26G-ISMS22 Amycolamicin, a Novel Antibiotic as a Promising Candidate for Clostridium Difficile
Infection: Antibacterial Activity, Mode of Action, and In Vivo Efficacy○ Yoshimasa ISHIZAKI1, Kazushige SASAKI1, Hideki HASHIZUME1, Chigusa HAYASHI1,
Kunio INOUE1, Hayamitsu ADACHI1, Yoshiaki TAKAHASHI1, Masayuki IGARASHI1,
Yoshio NISHIMURA1, Yuzuru AKAMATSU1, Akio NOMOTO1, Masakatsu SHIBASAKI1
1（ Institute of Microbial Chemistry (BIKAKEN)）

26G-ISMS23 Identification and Optimization of a Novel Series of Tetrahydroisoquinoline Derivatives
as an Orally Active MGAT2 Inhibitor○ Tsuyoshi BUSUJIMA1, Hiroaki TANAKA2, Eiji MUNETOMO3, Kiyokazu KITANO3,
Masako SAITO3（1Pharamceutical Science Laboratories, 2Chemistry Laboratories, 3Pharmacology Laboratories,
Taisho Pharmaceutical Co., Ltd.）– 20 –

26G-ISMS24 Discovery of Novel Fluoroquinolone Antibiotics WFQ-101 and Its Optimization Study○ Tatsuya HIRANO1, Tomohiko KINOSHITA1, Daichi KAZAMORI1, Satoshi INOUE1,
Kouji NISHIMURA1, Asuka SAKURAI1, Ayuka SASAKI1, Yasuhiro KURAMOTO1,
Hirotaka AMANO1, Akira YAZAKI1（1Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd.）
26G-ISMS25 Anti-CTLA-4 Antibody scFv Producing Recombinant Bifidobacterium Secretes CTLA4 Blocker Specifically Inside Hypoxic Tumor and Suppresses Tumor Growth inSyngeneic Mice Model○ Shiro KATAOKA1, Koichiro SHIOYA1, Li WANG1, Tomio MATSUMURA1,
Hitomi SHIMIZU1, Yasuyoshi KANARI1, Yuji SEKI1, Yuko SHIMATANI1,
Minoru FUJIMORI2, Shun'ichiro TANIGUCHI3（1Anaeropharma Science, Inc., 19-8, Nihonbashi Kabuto2cho, Chuo-ku, Tokyo 103-0026, Japan, Department of Breast Surgery, Tokyo Medical University Ibaraki Medical
3
Center, Ibaraki, Japan, Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine）

26G-ISMS26 Structural Basis for Activation of Neisseria Meningitides Elongation Factor P with
Arginine-32 Rhamnosylation by EarP
○ Toru SENGOKU1（1RIKEN Structural Biology Laboratory）
26G-ISMS27 Design, Synthesis and Biological Evaluation of a Novel Series of Peripheral-selective
Noradrenaline Reuptake Inhibitor, Part I -Lead Series Discovery and Biological
Concept Validation○ Ikuo FUJIMORI1, Tomoya YUKAWA1, Taku KAMEI1, Yoshihisa NAKADA1,
Nobuki SAKAUCHI1, Masami YAMADA1, Yusuke OHBA1, Maiko TAKIGUCHI1,
Masako KUNO1, Izumi KAMO1, Hideyuki NAKAGAWA1, Teruki HAMADA1,
Tomoko IGARI1, Teruaki OKUDA1, Satoshi YAMAMOTO1, Tetsuya TSUKAMOTO1, Yuji
ISHICHI1, Hiroyuki UENO1（1Takeda Pharmaceutical Company Limited）
26G-ISMS28 Design, Synthesis and Biological Evaluation of a Novel Series of Peripheral-selective
Noradrenaline Reuptake Inhibitor, Part II -Lead Optimization with Avoiding P-gp
Substrate and Genetic Polymorphism○ Tomoya YUKAWA1, Ikuo FUJIMORI1, Taku KAMEI1, Yoshihisa NAKADA1,
Nobuki SAKAUCHI1, Masami YAMADA1, Yusuke OHBA1, Hiroyuki UENO1,
Maiko TAKIGUCHI1, Masako KUNO1, Izumi KAMO1, Hideyuki NAKAGAWA1,
Yasushi FUJIOKA1, Tomoko IGARI1, Yuji ISHICHI1, Tetsuya TSUKAMOTO1
1（ Takeda Pharmaceutical Company Limited）

26G-ISMS29 Ex Vivo Gene-manipulated Mature Adipocytes: Novel Gene Therapy Medicine for
Sustained Protein Replacement Therapy of Variety of Intractable Diseases○ Masayuki KURODA1, Hideaki BUJO2, Koutaro YOKOTE3, Yasushi SAITO4,
Masayuki ASO5（1Center for Advanced Medicine, Chiba University, 2Department of Clinical Laboratory
3

Medicine, Toho University Medical Center Sakura Hospital, Department of Clinical Cell Biology and Medicine,
4
Graduate School of Medicine, Chiba University, Superintendent of the hospital bureau, City Hall of Chiba,
5CellGenTech, Inc.）

26G-ISMS30 Application of Novel Highly Immunodeficient Mice for Patient Derived Xenograft(PDX) Model and Evaluation of Anticancer Therapy○ Seiji OKADA1, Kulthida VAETEEWOOTTACAHRN1, Hiroki GOTO1, Ryusho KARIYA1
1（ Center for AIDS Research and Graduate School of Medical Sciences, Kumamoto University）

26G-ISMS31 The Unbound Concentration of Multimodal Drugs in the Assay Medium Used in theMulti-electrode Array System for Cardiac Risk Assessment with iPS Cell-derived
Cardiomyocytes○ Takashi YOSHINAGA1,4, Raku SINKYO2, Kiyomi KIKUCHI2, Tomohiko TANIGUCHI1,4,
Yuko SEKINO3,4, Kohei SAWADA1,4（1Global CV Assessment, Eisai Co., Ltd., 2Global DMPK, Eisai Co., Ltd.,
3

4

Division of Pharmacology, National Institute of Health Sciences, Japan iPS Cardiac Safety Assessment (JiCSA)）– 21 –

26G-ISMS32 Discovery of ASP3026, a Potent and Selective Anaplastic Lymphoma Kinase (ALK)
Inhibitor○ Kazuhiko IIKUBO1, Yutaka KONDOH1, Itsuro SHIMADA1, Takahiro MATSUYA1,
Kenichi MORI1, Yoko UENO1, Sadao KUROMITSU1, Minoru OKADA1（1Astellas Pharma Inc.）
26G-ISMS33 Immune Profiling with a New NGS-based Repertoire Analysis○ Takaji MATSUTANI1, Kazutaka KITAURA1, Hiroshi YAMASHITA1, Hitomi AYABE1,
Hiroyuki SATO1, Yuichi MORITA1, Tadasu SHINI2,3, Ryuji SUZUKI1,3（1Repertoire Genesis
2

3

Incorporation, BITS. Co., Ltd., Clinical Research Center for Rheumatology and Allergy, Sagamihara National
Hospital）

26G-ISMS34 Cyclodextrin-based Supramolecular Drug Carriers and Active Pharmaceutical
Ingredients○ Taishi HIGASHI1, Keiichi MOTOYAMA1, Hidetoshi ARIMA1,2（1Department of Physical2

Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Program for Leading Graduate
Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program”, Kumamoto University）

26G-ISMS35 Antifungal Activities and Nonclinical Pharmacokinetics of APX001A/APX001 (E1210/
E1211), a New Broad-Spectrum Antifungal, with a New Mode of Action○ Takaaki HORII1（1Global Health Research Section, hhc Data Creation Center, Eisai Co., Ltd.）
26G-ISMS36 Synthesis and Evaluation of Potent, Orally Available, Well-balanced EP2 and EP3 Dual
Agonists○ Akihiro KINOSHITA1, Masato HIGASHINO1, Koji YOSHIDA1, Yoshiyuki ARATANI1,
Akito KAKUUCHI1, Keisuke HANADA1, Hiroyuki TAKEDA1, Toshikiko NISHIYAMA1,
Hidekazu MATSUYA1, Kazuyuki OHMOTO1（1Medicinal Chemistry Research Laboratories, Ono
Pharmaceutical Co., Ltd.）

26G-ISMS37 Novel Development of Chemotherapy for Relapsed and Refractory AML Based on thePromising Functional Mechanism of Cytidine Analog, DFP-10917○ Masakazu FUKUSHIMA1, Kenzo IIZUKA1, Chung ZHANG1, Cheng JIN1, Kiyoshi ESHIMA1
1（ Division of Research and Development, Delta-Fly Pharma, Inc.）

26G-ISMS38 System-wide Temporal Characterization of the Phosphoproteome of Non-small-cell
Lung Cancer Cells Treated with Erlotinib○ Adachi JUN1, Yuichi ABE1, Maiko SHIMIZU1, Marina KISHIDA1, Ayako SATO1,
Takeshi TOMONAGA1（1Laboratory of Proteome Research National Institutes of Biomedical Innovation,
Health and Nutrition）

26G-ISMS39 Identification of WAC-224, a Novel Anticancer Quinolone as a Human Topoisomerase
II Inhibitor○ Tomonori YAMAGUCHI1, Kenji ITOH1, Taichi UESHIMA1, Rumiko SHIMABARA1,
Yohei KAWAKUBO1, Masayuki SATO1, Junpei YAMASHITA1, Tatsuya HIRANO1,
Akira YAZAKI1（1Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd.）
26G-ISMS40 Lenvatinib Mesilate (LEN) Enhanced Antitumor Activity of a PD-1 Blockade Agent byPotentiating Th1 Immune Response○ Yu KATO1, Xingfeng BAO2, Shannon MACGRATH2, Kimiyo TABATA1, Yusaku HORI1,
Sho TACHINO1, Mark MATIJEVICI2, Yasuhiro FUNAHASHI1, Junji MATSUI1（1Eisai Co., Ltd.,
2

Tsukuba, Ibaraki, Japan, Eisai Inc. Andover, MA, USA）

26G-ISMS41 Identification of Blood-based Gene Expression Biomarkers for Major Depressive and
Bipolar Disorders○ Seiji NAKAMURA1, Hiroaki HORI2, Yohei ISHIZAWA1, Kenichi MATSUBARA1,
Ryo MATOBA1, Hiroshi KUNUGI2（1DNA Chip Research Inc., 2Department of Mental Disorder Research,
National Institute of Neuroscience, National Center of Neurology and Psychiatry）– 22 –

26G-ISMS42 Anti-Helicobacter Pylori Activity of a Novel Derivative of Intervenolin○ Tomokazu OHISHI1, Toru MASUDA1, Shun-ichi OHBA1, Chigusa HAYASHI2,
Hikaru ABE3, Masayuki IGARASHI2, Takumi WATANABE3 , Daniel Ken INAOKA4,
Kiyoshi KITA5, Masakatsu SHIBASAKI3, Manabu KAWADA1,6（1Institute of Microbial Chemistry
2(BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Institute of Microbial Chemistry (BIKAKEN),
3
Laboratory of Microbiology, Microbial Chemistry Research Foundation, Institute of Microbial Chemistry (BIKAKEN),
4
Laboratory of Synthetic Organic Chemistry, Microbial Chemistry Research Foundation, Center for International
5
Collaborative Research, Nagasaki University, School of Tropical Medicine and Global Health, Nagasaki University,
6
Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation）

26G-ISMS43 Discovery of Novel 5,6,7,8-tetrahydro[1,2,4]Triazolo[4,3-a ]Pyridine Derivatives asγ-secretase Modulators○ Takafumi TAKAI1, Tatsuki KOIKE1, Minoru NAKAMURA1, Yasutaka HOASHI1,
Yoshihide TOMATA1, Sachie MORIMOTO1, Yuichi KAJITA1, Toshiro YAMASHITA1,
Naohiro TAYA1, Tetsuya TSUKAMOTO1, Tomomichi WATANABE1, Koji MURAKAMI1,
Tomoko IGARI1, Makoto KAMATA1（1Takeda Pharmaceutical Company Limited）
26G-ISMS44 Regulatory Science for R&D Promotion of Innovative Pharmaceuticals*
Kazuhiko MORI1, Takao YAMORI2, ○ Toru KAWANISHI3, Takao INOUE4（1Ministry of Health,2

3

Labor and Welfare (MHLW), Pharmaceuticals and Medical Devices Agency (PMDA), National Institute of Health4
Sciences (NIHS), Japan Agency Medical Research and Development (AMED)）– 23 –

6 Abstracts
3rd International Symposium for Medicinal Sciences
Akira OTAKA

Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University

The objectives of this symposium are to encourage pharmaceutical company researchers who areinterested in drug discovery to participate in this annual meeting, and also to create an importantinternational platform for all those interested in the medicinal sciences. Since this symposium covers
the entire drug discovery field, we welcome participants from disciplines including pharmacology,
pharmacokinetics, and regulatory sciences.
One of the features of this symposium is a wide array of invited poster presentations. Since the program
will include high-caliber presentations from the Japanese and foreign pharmaceutical industries,
venture companies, and academia, young Japanese researchers who are interested in drug discovery
will have valuable opportunities for discussion with ﬁrst-class drug discovery researchers from aroundthe world.

Plenary Lecture 1

Tachibana Conference Hall 10:45−11:45

ISMS-PL01 Robot Scientists: Automating Drug Design
Ross D. KING
University of Manchester

A Robot Scientist is a physically implemented robotic system that applies techniques from
artificial intelligence to execute cycles of automated scientific experimentation. A Robot Scientist
can automatically execute cycles of: hypothesis formation, selection of efficient experiments todiscriminate between hypotheses, execution of experiments using laboratory automation equipment,
and analysis of results. The motivation for developing Robot Scientists is to better understand science,and to make scientiﬁc research more efﬁcient. The Robot Scientist ʻAdamʼ was the ﬁrst machine toautonomously discover novel scientific knowledge. Our new Robot Scientist, ʻEveʼ, is designed toautomate and integrate drug screening, hit conformation, and QSAR development. Its combination ofnovel automation with synthetic biology assays enables faster and cheaper drug design. Eveʼs focus
was originally on neglected tropical diseases, and Eve has discovered hits and leads against targets in
multiple parasites. We are now adapting Eve to work with and learn about human cancer cell lines.
There is currently a ʻreplication crisisʼ in biology, and many scientific results have been shown to
difﬁcult to replicate. We argue that the formalisation of protocols, combined with the automation ofexperiments, is the best way to replicate results.

– 24 –

Plenary Lecture 2

Tachibana Conference Hall 13:15−14:15

ISMS-PL02 Recent Advances in cryo-EM: Applications to Drug Discovery
Sriram SUBRAMANIAM
National Cancer Institute, NIH

Recent breakthroughs in the field of cryo-electron microcopy (cryo-EM) provide new prospects fordetermination of the structures of a variety of macromolecular assemblies and offer unprecedented
opportunities for drug discovery. The prospect that the determination of protein structures to atomic
resolution will no longer be limited by size, or by the need for crystallization represents a signiﬁcantand exciting horizon in structural biology. I will discuss the application of these methods to analyze
structures of a variety of biologically and medically relevant multi-protein complexes and membraneprotein assemblies, which have historically represented the most challenging frontier in structural
biology.
Selected publications:• Merk A., Bartesaghi A, Banerjee S, Falconieri V, Rao P, Davis M, Pragani R, Boxer M, Earl LA,
Milne JLS, Subramaniam S (2016) Breaking cryo-EM resolution barriers to facilitate drug discovery.
Cell, 165 1698-1707.
• Matthies D, Dalmas, O, Borgnia, MJ, Dominik, PK, Merk, A, Rao, P, Reddy, BG, Islam, S.,
Bartesaghi, A, Perozo, E, Subramaniam, S (2016) Cryo-EM Structures of the Magnesium Channel
CorA Reveal Symmetry Break Upon Gating. Cell, 164, 747-756.
• Banerjee, S, Bartesaghi, A, Merk, A, Rao, P. Bulfer, SL, Yan, Y, Green, N, Mroczkowski, B, Neitz,
RJ, Wipf, P, Falconieri, V, Deshaies, RJ, Milne, JLS, Huryn D, Arkin, M, Subramaniam S (2016) 2.3 Å
resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science, 351,871875.
• Meyerson JR, Chittori S, Merk A, Rao P, Han TH, Serpe, M, Mayer ML, Subramaniam S (2016)
Structural basis of kainate subtype glutamate receptor desensitization. Nature 537:567-571.
• Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JLS, Subramaniam S (2015) 2.2 Å resolution
cryo-EM structure of β -galactosidase in complex with a cell-permeant inhibitor. Science 348:1147-1151.

– 25 –

Invited Poster Presentation
Short Presentation
Discussion

Tachibana Conference Hall 14:20−16:00
Meeting Room 4

Odd Number: 16:00−16:50 / Even Number: 16:50−17:40

26G-ISMS01 Unstructured Protein : A New Approach for Drug Discovery○ Takenao ODAGAMI1, Yoichiro HIROSE1, Yoshimasa IMAMURA1, Akira KATOH1,
Tadashi MISHINA1, Hiroyuki KOUJI1
1

Research & Development, PRISM BioLab Co., Ltd.

There are many successful examples in drug discovery of developing enzyme inhibitors and receptor
agonists/antagonists. However, attempts to develop modulators of protein/protein interaction havelargely been unsuccessful. This is especially true in developing modulators for transcription factors andfor doing so with small molecules.
Helix structures are prevalent and are often observed in intracellular protein/protein interactions.
PRISM has designed novel compounds based on helix structures and has developed small to middle
size molecules exhibiting strong activity in modulating critical intracellular protein/protein interaction.
In case of intracellular protein/protein interaction, unstructured (intrinsic disorder) region plays animportant role for their binding. The 50% of intracellular protein was estimated to have unstructured
region. Intrinsic disorder region is highly abundant among proteins associated with various humandiseases such as cancer, metabolic diseases, and cardiovascular diseases. However, systematic approachto target unstructured/structured protein/protein interaction has not been done in drug discovery
area, to the best of our knowledge. PRISM focused on the protein/protein interaction to explore drugcandidates. PRISM platform has resulted in a clinical-stage program based on targeting the CBP/betacatenin complex, as well as other preclinical drug development programs.
We would like to discuss here PRISMʼs platform technology that focused on unstructured/structured
protein/protein interaction to explore drug candidates.

26G-ISMS02 Development of Macrocyclic Peptide Targeting Ebola Glycoprotein○ Shiori UMEMOTO1, Junki MARUYAMA2, Ayato TAKADA2, Hiroaki SUGA1
1
2

Department of Chemistry, Graduate School of Science, The University of Tokyo,
Department of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University

Ebola virus (EBOV), a member of the ﬁlovirus family, causes severe hemorrhagic fevers with 50-90%
lethality. The EVOV glycoprotein (GP) is the sole virally expressed protein on the virion surface andis essential for attachment to the host cell and for membrane fusion. Hence, the EBOV GP is a critical
drug target for combatting ebola virus. However, a truncated GP variant (sGP) that is secreted from
infected cells may act as a decoy for drug candidate. As a result, high afﬁnity and speciﬁcity, such as an
antibody, is required for any drug targeting EBOV. We have previously developed a system, known as
the RaPID system, to evolve macrocyclic peptides that speciﬁcally and strongly bind to a target protein
and regulate function of the protein. The RaPID system combines ribosomal expression of a peptide
library including non-proteogenic amino acids with ribosomal display, allowing expression of vast
macrocyclic peptide libraries of up to trillions of macrocyclic peptides. In this poster, we introduce
our strategy to develop macrocyclic peptides that bind to EBOV GP, the most potent of which has adissociation constant of 6.3 nM, which is comparable of that of an antibody. The small size and potencyof these macrocyclic peptides will give a big advantage in choice of strategies for functionalization, as
well as easier handling and large scale production. They may therefore open up new strategy to combat
EBOV.

– 26 –

26G-ISMS03 Combinatorial Solid-Phase Synthesis and Biological Evaluation of

Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast
Morphology○ Hiroshi SATO1,2, Masahito YOSHIDA1, Hayato MURASE3, Hiroshi NAKAGAWA3,

Takayuki DOI1
1
3

Graduate School of Pharmaceutical Sciences, Tohoku University, 2Mitsubishi Tanabe Pharma Corporation,
Department of Applied Biological Chemistry, Chubu University

Cyclodepsipeptide destruxins were firstly isolated from Metarhizium anisopliae , and consist ofﬁve amino acids (β-Ala, L-MeAla, L-MeVal, L-Ile, and L-Pro) and an α-hydroxy acid derivative.1 In
particular, destruxin B (1) that possesses an isobutyl moiety as a side-chain on an α -hydroxy acidderivative, reversibly inhibits bone-resorbing activity of osteoclasts without affecting cell viability.2
Therefore, destruxins can be a promising candidate for developing novel anti-resorptive agents.
Because of structural and biological properties of 1, combinatorial synthesis and biological evaluationof cyclodepsipeptide destruxin B (1) were demonstrated.3 We designed 64-member analogues towardelucidation of structure-activity relationships, and the cyclization precursors were readily prepared bysolid-phase peptide synthesis using a split and pool method. After cleavage from the polymer-support,
macrolactonization utilizing MNBA-DMAPO in the solution phase was successfully performed inparallel to afford desired destruxin analogues in moderate to good yields. In this presentation, details ofcombinatorial synthesis and biological evaluation of the synthesized analogues will be discussed.
References
1. Païs, M.; Das, B. C.; Ferron, P. Phytochemistry 1981, 20 , 715 − 723.
2. Nakagawa, H.; Takami, M.; Udagawa, N.; Sawae, Y.; Suda, K.; Sasaki, T.; Takahashi, N.; Wachi, M.;
Nagai, K.; Woo, J. T. Bone 2003, 33 , 443 − 455.
3. Sato, H.; Yoshida, M.; Murase, H.; Nakagawa, H.; Doi, T. ACS Comb. Sci, 2016, 18 , 590-595.

26G-ISMS04 SAR Exploration of Selective Kinase Inhibitors based on the “Head-to-Tail”
Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds○ Satoru NOJI1, Noriyoshi SEKI1, Takaki MAEBA1, Takayuki SAKAI1, Eiichi WATANABE1,
Katsuya MAEDA1, Kyoko FUKUSHIMA1, Toru NOGUCHI1, Kazuya OGAWA1,
Yukiyo TOYONAGA1, Tamotsu NEGORO1, Hisashi KAWASAKI1, Makoto SHIOZAKI1
1

Central Pharmaceutical Research Institute, Japan Tobacco Inc.

In typical kinase inhibitor programs, a hinge binder showing best potency with preferential speciﬁcity
is initially selected, followed by fine-tuning of the accompanying substituents on its core module.
A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all
the analogues in the series if a critical drawback is revealed. Thus, an early effort to prepare such a
potential risk by having a multiple series of compounds is rationalized, although there have been very
few examples to follow such a policy. PI4KIIIα is one of four mammalian phosphatidylinositol-4
kinases and has recently drawn signiﬁcant attention as an emerging target for hepatitis C virus (HCV)
treatment. Inhibition of this host factor seems to provide a higher barrier to vial resistance as well asactivity against all existing HCV genotypes. In this presentation, a novel “Head-to-Tail” approach todiscover a diverse set of PI4KIIIα inhibitors is reported. We believe this method will generate distinct
core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.

– 27 –

26G-ISMS05 Search for Anti-leukemic Drugs Targeting the Transcription Factor Runx1 by

INTENDD○ Masaaki SHIINA1, Shiho BABA1, Akiko UCHIYAMA1, Chikako OKADA1,

Takeshi TANAKA2, Ken IKEDA2, Shigetsugu KAWAKITA2, Takao MATSUZAKI2,
Hirotsugu KOMATSU2, Masato HOSODA2, Kazuhiro OGATA1
1

Yokohama City University, Graduate School of Medicine, 2Interprotein Corporation

Advance in the molecular targeted therapy has dramatically changed and improved a treatment of cancer. However, its
narrow target spectrum and acquired drug resistance in tumors remain to be solved. These problems partly stem fromthe limited variation of the targeted molecules; almost all have been protein kinases. To settle the problems, a promising
way is to develop drugs targeting proteins other than kinases. One of the potential targets is a transcription factor
because its mutation is known to be frequently involved in cancer development. However, transcription factors do nothave any enzymatic activity themselves, and thus the compounds necessarily target the molecular interactions involved,
which is quite challenging. This may explain why few drugs targeting transcription factors have been available as longas we know.
Our present research goal is to develop anti-leukemic drugs targeting a transcription factor, Runx1. Runx1 is known asa master regulator of the blood cell development, and various mutations of Runx1 gene have frequently been found inacute myeloblastic leukemia (AML) patients, leading to belief that Runx1 is an assured drug target for AML. Because
Runx1 binds target gene enhancers as a heterodimer with CBFβ to regulate transcription, the desired compounds arelikely to target the interactions of Runx1 with DNA or CBFβ .
We started our challenge with a unique type of in silico screening, INTENDD, which was developed by
INTEPROTEIN CORP. and stands for INTerproteinʼs Engine for New Drug Design. In this method, we eyeball a real
3D model produced by a 3D printer based on a protein structure to ﬁnd a molecular pocket for small compounds. Then,in silico screening is performed just for the candidate pockets. With INTENDD, we found and picked up 167 and142 compounds targeting Runx1-DNA and Runx1-CBFβ interactions, respectively. Then we evaluated the inhibitory
activity of the found compounds against DNA binding of Runx1 using surface plasmon resonance (SPR). We had
totally 49 positive compounds, 3 of which strongly inhibited DNA binding of Runx1 with IC50 below 1 µM. We haveveriﬁed that some of the positive compounds bind to Runx1 with the comparable afﬁnity (K D: 0.01-10 µM range).

26G-ISMS06 Evaluation of Novel Anti-Dengue Candidates Using In Silico and In Vitro

Approaches○ Yu-Shi TIAN1, Hitoshi MATSUDA2, Xinzhe LIU2, Norihito KAWASHITA2,3,

Tatsuya TAKAGI2,3
1

Graduate School of Information Science and Technology, Osaka University,
Graduate School of Pharmaceutical Sciences, Osaka University,
3
Graduate School of Information Science and Technology, Osaka University Research Institute forMicrobial Diseases
2

Dengue virus or DENV belongs to the family Flaviviridae and is mediated by mosquitoes. Most
patients appear in tropical and sub-tropical regions. Recently due to the climate change and theincrease of global travelers, the regions of DENV infections are no more limited and being enlarged.
The infections accompanying with hemorrhagic fever and/or shock syndrome became serious issues,
especially when patients were infected by a different serotype of DENV for the second time. Although
fruity studies on DENV have been carried out, so far no potent vaccine or antiviral drug has been
approved [1]. We reported SK-12 in 2013 as a novel active molecule which is considered to target theinteraction between non-structured viral proteins NS2B and NS3 [2]. In the current study, we look backinto NS3/NS2B protease, a famous target for anti-Dengue study. We used high-throughput screening
technique and In Silico studies to search for active candidates from compound libraries obtained from
Osaka University. We found several candidates showed anti-DENV activities. Subsequently, thesecompounds were carefully checked to compare with previously reported molecules. Based on the mostpromising candidate, a screening of novel commercial libraries were carried out to solve time consume.
We will present our results in the poster section and are looking afford for deep discussions.
[1] (One example) Lai H. et al . Bioorg. Med. Chem. 21 102–113 2013.
[2] Pambudi S. et al . Biochem. Biophys. Res. Commun. 440 (3) 393-398 2013.
– 28 –

26G-ISMS07 Development and Construction of an Original Compound Library for CNS

Drug Discovery: Combining Computational and Wet Data to Enhance CNS
Drug-likeness○ Daiju HASEGAWA1
1

Medicinal Chemistry, Neurology Tsukuba Research Department, Discovery, Medicine Creation,
Neurology Business Group, Eisai Co., Lid.

High quality HTS hits are important for drug discovery programs to accelerate medchem campaign toclinical candidate and improve the overall success rate in the drug development. To provide such highquality HTS hits, sophisticatedly designed compound libraries play an important role in HTS strategy.
In addition, a compound library with enhanced CNS drug-likeness (good brain penetrability and goodoral availability) should improve the productivity of drug discovery programs in the neuroscience area.
Against this background, we have been constructing a CNS-focused compound library by:• Innovative design to improve the probability of the compounds reaching the CNS.
• Extensive in vitro , in vivo and physicochemical characterization of library members to eliminate
structures with inherent liabilities.
• Newly-designed compounds based on structurally novel scaffolds.
In this poster, we describe our strategy for constructing a CNS-focused compound library utilizing the
combination of a computational scoring system and in vitro/in vivo DMPK data. In addition, we also
describe how we gathered our original scaffold collection to emphasize structural novelty in the library.

26G-ISMS08 Structure-based Design, Synthesis, and Biological Evaluation of Imidazo[1,2-b ]Pyridazine- based p38 MAP Kinase Inhibitors○ Akira KAIEDA1, Masashi TAKAHASHI1, Takafumi TAKAI1, Masayuki GOTO1,

Takahiro MIYAZAKI1, Yuri HORI1, Satoko UNNO1, Tomohiro KAWAMOTO1, Toshimasa
TANAKA1, Sachiko ITONO1, Terufumi TAKAGI1, Teruki HAMADA1, Mikio SHIRASAKI1,
Kengo OKADA1, Gyorgy SNELL2, Ken BRAGSTAD2, Bi-Ching SANG2, Osamu
UCHIKAWA1, Seiji MIWATASHI1
1

Takeda Pharmaceutical Company Limited, 2Takeda California, Inc.

We have identiﬁed a novel series of potent p38 MAP kinase inhibitors through structure-based design
strategy. In the X-ray co-crystal structure of p38 MAP kinase with TAK-715 (1), Phe169 adopts two
conformations that one interacts with 1 and the other shows no interaction with 1. Our structure-based
design strategy is that these two conformations converge on one conformation by enhancement of theprotein-ligand hydrophobic interaction. Scaffold transformation was conducted to enhance the proteinligand hydrophobic interaction to resulting in the identiﬁcation of imidazo[1,2-b ]pyridazine derivatives
as a lead series of potent p38 MAP kinase inhibitors, followed by investigation of structure and DMPK
profile relationship. We provide a rational design, synthesis, SAR studies, and biological studies ofimidazo[1,2-b ]pyridazine derivatives.

– 29 –

26G-ISMS09 Flow Chemistry: New Horizons in Chemical Space for the Creation of Next

Generation Libraries

Daniel BLANCO-ANIA3, Sagar Ashok GAWADE1, Luuk MAARTENSE1,
Roel VERLEIJSDONK1, Remco MERKX2, Huib OVAA2, Floris RUTJES1,
Marjon BOLSTER3, Luc ZWINKELS3, Joeri SCHEIDT3, Pauline van MEURS3,
Jorg BENNINGSHOF3, ○ Norimasa MORITA3
1

Radboud University, 2Leiden UMC (Former NKI), 3MercachemAs a member of the European Lead Factory (ELF), Mercachem is responsible for generation,
validation and production of libraries consisting of ~10,000 compounds from ~20 scaffolds per year.
This poster presents two examples where continuous flow chemistry facilitated the synthesis ofscaffolds (and their corresponding libraries) with limited accessibility in batch processes. First, a 700
membered imidazolidinone library was smoothly prepared by the generation and subsequent reductionof an unstable and explosive azide keyintermediate in ﬂow. Secondly, photochemistry in ﬂow enabled
the construction of two conformationally restricted three-dimensional aminoketone scaffolds at large
scale in unprecedented efﬁciency.

26G-ISMS10 Transition Metal-Free, Tryptophan-Selective Bioconjugation of Proteins○ Kounosuke OISAKI1, Yohei SEKI1, Takashi ISHIYAMA1, Daisuke SASAKI1,2,
Junpei ABE1, Yohei SOHMA1,2, Motomu KANAI1,2
1
2

Graduate School of Pharmaceutical Sciences, The University of Tokyo,
JST, ERATO Kanai Life Science Catalysis ProjectChemical modiﬁcations of native proteins can facilitate production of supernatural protein functions
that are not easily accessible by complementary methods relying on genetic manipulations. Even
though precise control over the chemo-, site, and modiﬁcation-number selectivity in protein chemical
conjugates with maintained structural integrity and homogeneity is highly important, it still represents
a major challenge. The available toolbox of native protein conjugations does not contain satisfactory
solutions to this challenge at present. In many cases, the conjugation sites are located at the side chainsof lysine and cysteine residues. Despite recent improvements, these methods often afford unsatisfactory
levels of selectivity with disintegrated higher-order structures.
We report a transition metal-free method for tryptophan-selective bioconjugation of proteins that isbased on an organoradical and operates under ambient conditions. This method exhibits low levels ofcross-reactivity and leaves higher-order structures of the protein and various functional groups therein
unaffected. The strategy to target less abundant amino acids contributes to the formation of structurally
homogeneous conjugates, which may even be suitable for protein crystallography. The absence of toxic
metals and biochemically incompatible conditions may thus easily ﬁnd therapeutic applications.

– 30 –

26G-ISMS11 Total Synthesis of Halichondrin A and C○ Akihiko YAMAMOTO1, Atsushi UEDA1, Paul BRÉMOND1, Paolo S. TISENI1,
Daisuke KATO1, Yoshito KISHI1
1

Department of Chemistry and Chemical Biology, Harvard University

The first total sythesis of Halichondrin A and C was achieved by utilizing multiple Cr-mediatedcoupling to form a new C-C bond*. Halichondrins A/C are C12- and C13-di-hydroxylated / C12hydroxylated form of Halichondrin B, whose right-half substructure led to the antitumor drug Eribulin(Figure 1 ). The syntheses are highlighted by the construction of C8-C14 polycyclic ketal for both A and
C (Figure 2 ).

* J. Am. Chem.Soc. 2014, 136 , 5171-5176, J. Am. Chem.Soc. 2012, 134 , 893−896

26G-ISMS12 Parallel Fluorescent Probe Synthesis Based on the Large-scale Preparation of

BODIPY FL Propionic Acid

○ Taisuke KATOH1, Masato YOSHIKAWA1, Takeshi YAMAMOTO1, Ryosuke ARAI1,

Noriyuki NII1, Yoshihide TOMATA1, Shinkichi SUZUKI1, Ryoukichi KOYAMA1,
Nobuyuki NEGORO1, Takatoshi YOGO1
1

Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd

We describe a methodology for quick development of ﬂuorescent probes with the desired potency
for the target of interest by using a method of parallel synthesis, termed as Parallel Fluorescent
Probe Synthesis (Parallel-FPS). BODIPY FL propionic acid 1 is a widely used fluorophore, but is
an expensive reagent, which hinders its use in parallel synthesis. Optimization of a synthetic scheme
enabled us to obtain 50 g of 1 in one batch. With this large quantity of 1 in hand, we performed
Parallel-FPS of BODIPY FL-labeled ligands for estrogen related receptor-α (ERRα). An initial trial of
the parallel synthesis with various linkers provided a potent ligand for ERRα (Reporter IC50 = 80 nM),demonstrating the usefulness of Parallel-FPS.

– 31 –

26G-ISMS13 Improvement in Pharmacokinetics and In Vivo Activity of Somatostatin by

Chemical Glycosylation○ Hirofumi OCHIAI1, Jun IGARASHI1, Hayato SAIJO1, Takahiro YAMAMOTO1,

Yuji NISHIUCHI1, Akio KANATANI1, Taiji SHIMODA1
1

GlyTech, Inc.

Somatostatin is naturally occurring peptide hormone that inhibits the secretion of several hormones
through the binding to five distinct receptor subtypes. Despite the wide variety of its activity,
therapeutic indications of native somatostatin are limited due to its short plasma half-life. In the present
study, we synthesized glycosylated somatostatin analogs by chemically attaching one to four complex
type sialyloligosaccharide chain(s) to the somatostatin molecule. The plasma half-life was extended
by approximately 10-fold by the attachment of a single glycan, and the half-lives were prolonged byincreasing the number of attached glycans. A single glycan-attached somatostatin maintained a highaffinity to all receptor subtypes as in the case of native somatostatin. Furthermore, the glycosylated
somatostatin demonstrated an efficient inhibition of growth hormone release in rats. These results
indicate that glycosylated somatostatin analogs could be a potent therapeutic drug candidate for several
diseases where somatostatin receptor subtypes are closely involved.

26G-ISMS14 Development of an Oxidative Mizoroki-Heck Reaction for Late-stage C-HFunctionalization of Complex Molecules and Application to Pharmaceutical
Studies○ Kenji WATANABE1, Amrita DAS1, Takumi KIMIJIMA1, Tomohiro YAMASHITA1,

Kazuhide INOUE1, Makoto TSUDA1, Takashi OHSHIMA1
1

Graduate School of Pharmaceutical Sciences, Kyushu University

Duloxetine, a serotonin and noradrenaline reuptake inhibitor, was recently found to inhibit P2X4
receptors in microglial cells, and reduce nerve injury-induced allodynia in rats.1) Therefore, chemical
modiﬁcation of duloxetine may lead to the development of a potent drug for treating neuropathic pain.
To synthesize a variety of duloxetine derivatives in a highly efficient way, we adopted a late-stage
C–H functionalization strategy. Our initial trials using conventional C–H activation methods, however,resulted in the elimination of the naphtoxy group of duloxetine by due to severe reaction conditions.
Therefore, we focused on the development of a new C–H activation reaction proceeding under neutral
and mild condition, and ﬁnally we achieved a selective oleﬁnation of the thienyl group of duloxetine
through catalytic oxidative Mizoroki-Heck reaction using molecular oxygen as the terminal oxidant.2)
Under the optimized reaction conditions, various alkenyl groups were introduced into duloxetine in ahighly regioselective manner. The obtained products were further transformed to various duloxetine
derivatives, some of which showed improved biologic activity. We further studied fundamental
reactivity of the reaction against various electron-rich arenes and hetero-arenes, and applied to latestage functionalizations of several natural and medicinal compounds to demonstrate the utility of thereaction for the construction of chemical libraries of complex molecules.
1) Yamashita, T.; Yamamoto, S.; Zhang, J.; Kometani, M.; Tomiyama, D.; Kohno, K.; Tozaki-Saitoh, H.;
Inoue, K.; Tsuda, M. PLOS ONE 2016, 11 (10): e0165189. doi:10.1371/ journal.pone.0165189.
2) Manuscript in preparation.
– 32 –

26G-ISMS15 Functional Characterization of Acetylcholine Receptors in Human

Hippocampus-Derived Neurons○ Kazuyuki FUKUSHIMA1, Kazuto YAMAZAKI2, Norimasa MIYAMOTO3,

Kohei SAWADA3
1

Neurology Tsukuba Research Department, Discovery, Medicine Creation, Neurology Business Group,
Eisai Co., Ltd., 2Technology Cross Point Laboratory, hhc Data Creation Center, Eisai Co., Ltd.,
3
Global CV Assessment, BA CFU, Medicine Development Center, Eisai Co., Ltd.

Utilizing human cell models mimicking physiologically- and/or disease-relevant conditions is a
key strategy to improve success rates in drug development. To apply the strategy to the CNS drug
development, it is essential to obtain functional human neurons. As a tool to generate functional
human neurons, we utilized human hippocampus-derived neural stem/progenitor cells (HIP-009 cells).
We previously demonstrated that HIP-009 cells can differentiate into neurons expressing glutamate
receptors functionally, and that they were applicable to assessment system of drug candidates forglutamate receptor-related neurological disorders including Alzheimerʼs disease (AD). In addition to
glutamate receptors, acetylcholine receptors (AChRs) are another target group for AD therapeutics.
Here, we examined the potential to apply HIP-009 neurons to functional assessment of drug candidates
targeting AChRs. qRT-PCR analysis revealed that expression of nicotinic (nAChR) and muscarinic
acetylcholine receptor (mAChR)-related genes was upregulated after four-week differentiation. Ca2+
ﬂux assays of HIP-009 neurons demonstrated that intracellular Ca2+ signals were increased by nicotine
and muscarine, indicating that HIP-009 neurons expressed nAChRs and mAChRs functionally. We also
pharmacologically investigated expression of each subtype by using subtype-selective compounds,
and identiﬁed functional expression of α7 and α4β2 nAChRs, as well as M1 and M3 mAChRs. These
results suggest that HIP-009 neurons are applicable to functional evaluation of drug candidates acting
on AChRs for AD drug development.

26G-ISMS16 Analgesic Effect of Novel 11 β -HSD1 Inhibitor ASP3662 and its Mechanism of

Action in a Spinal Nerve Ligation Model of Neuropathic Pain

○ Tetsuo KISO1, Toshihiro SEKIZAWA1, Mina TSUKAMOTO1, Junko YARIMIZU1,

Shuichiro KAKIMOTO1
1

Drug Discovery Research, Astellas Pharma Inc.

Glucocorticoids exert their effects via glucocorticoid receptors (GRs), and the central GR is reportedly involved in
the mechanism of neuropathic pain. 11β -hydroxysteroid dehydrogenase 1 (11β -HSD1) is involved in the conversionof inactive glucocorticoids to active glucocorticoids and is expressed not only in peripheral tissues but also in thecentral nervous system (CNS), such as brain and spinal cord. However, what role̶if any̶11β -HSD1 plays in paintransmission remains unclear. ASP3662 is a novel 11β -HSD1 inhibitor discovered through our research. Here, weinvestigated the analgesic effect and mechanism of ASP3662 in a spinal nerve ligation (SNL) model of neuropathic
pain in rats. In SNL model rats, the left L5 and L6 spinal nerves were tightly ligated with silk thread. For intrathecal
administration, the catheter was inserted between the L5 and L6 vertebrae. In the microdialysis experiment, the spinal
cord dialysis probe was passed transversely through the dorsal spinal cord via bilateral holes made through vertebra L1.
The mechanical threshold was determined by the von Frey hair test. ASP3662 concentrations in plasma and brain were
determined via liquid chromatography-tandem mass spectrometry. One week after spinal nerve ligation, mechanicalthresholds of the operated-side hindpaw were clearly lower than those in the sham group (mechanical allodynia). Single
oral doses of ASP3662 signiﬁcantly ameliorated mechanical allodynia, with an ED50 value of 0.087 mg/kg at 2 h afteradministration. Intrathecally administered ASP3662 also alleviated mechanical allodynia. A pharmacokinetics study
using SNL model rats revealed CNS penetration by this compound. In a microdialysis experiment, intraperitoneallyadministered corticosterone, the active glucocorticoid in rodents, signiﬁcantly increased spinal glutamate concentrations
in normal rats. Intraperitoneally administered 11-dehydrocorticosterone (11-DHC), the inactive glucocorticoid inrodents, significantly increased spinal glutamate concentrations in an SNL model but not in normal rats. ASP3662
signiﬁcantly inhibited this 11-DHC-induced increase in glutamate. ASP3662 is a novel, CNS-penetrable 11β -HSD1
inhibitor which alleviates mechanical allodynia in SNL rats. These results suggest that this compound is a promising
candidate for use in treating neuropathic pain. One site of action of ASP3662 is the spinal cord. This compound may
block glucocorticoid-induced increases in spinal glutamate concentration in SNL model rats by inhibiting conversion of
inactive glucocorticoids into active ones.

– 33 –

26G-ISMS17 Atomic-Scale Investigation on Acetaminophen Crystals with Stable and Metastable

Phases by Frequency Modulation Atomic Force Microscopy in Aqueous Solution○ Naritaka KOBAYASHI1, Kazuki OKANO2, Yoichiro MORI3, Shun FUKUKITA3,

Mihoko MARUYAMA4, Hiroaki ADACHI3,5, Kazufumi TAKANO4,5, Satoshi MURAKAMI5,6,
Hiroyoshi MATSUMURA5,7, Tsuyoshi INOUE3,5, Masashi YOSHIMURA5,8, Yusuke MORI3,5,
Seiichiro NAKABAYASHI1, Hiroshi YOSHIKAWA1,3
1

Graduate School of Science and Engineering, Saitama University, 2Faculty of Science, Saitama University,
Graduate School of Engineering, Osaka University, 4Graduate School of Life and Environmental Sciences,
Kyoto Prefectural University, 5SOSHO, Inc., 6Graduate School of Bioscience and Biotechnology, Tokyo
Institute of Technology, 7College of Life Science, Ritsumeikan University, 8Institute of Laser Engineering,Osaka University
3

Selective crystallization methods of metastable phase of medicinal organic compounds have been
being developed to improve bioavailability in pharmaceutical application. These crystals are often
grown from liquid phase. Therefore, it is quite useful for acceleration of the development to understandatomic-scale processes at crystal-solution interfaces.
Frequency modulation atomic force microscopy (FM-AFM) is a powerful tool that can image
surface structures with atomic resolution in liquid. FM-AFM has recently enabled us to visualize
water molecules localized at solid-liquid interfaces by measuring 3D force distribution. The water
distribution is called as hydration structure, which plays important roles in crystal growth. We havebeen investigating atomic-scale surface processes of acetaminophen (paracetamol) crystals with stable(Form I, monoclinic) and metastable (Form II, orthorhombic) phases by home-built atomic-resolution
FM-AFM.
We succeeded in obtaining atomic resolution images of Form I and II by imaging during theirdissolution in nearly-saturated solutions. This is the ﬁrst demonstration of atomic resolution imaging ofsoluble meta- stable crystal. We also revealed subnanoscale hydration structures formed on the surfacesof Form I and II.

26G-ISMS18 Anti-inﬂammatory Flavan-dihydrochalcones with Unprecedented Carbon

Skeletons from Daemonorops Draco○ Ping-Chung KUO1, Hsin-Yi HUNG1, Tsong-Long HWANG2, Tian-Shung WU1
1School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan, 2 Graduate Institute of Natural Products, College of Medicine, Chang Gung University

Four flavan-dihydrochalcones with unprecedented carbon skeletons, dragonins A-D (1-4) werecharacterized from the traditional Chinese medicine Sanguis Draconis. The structures of 1-4 were
elucidated by spectroscopic and spectrometric analyses. Compounds 1 and 2 exhibited significant
inhibition of fMLP/CB induced superoxide anion generation and elastase release. These puriﬁed ﬂavandihydrochalcones are potentially new leads for anti-inﬂammatory drug development.

– 34 –

26G-ISMS19 Development of a Fully Automated HPLC System (ASAPrepTM) Designed forMultiple Compound Puriﬁcations○ Chie KUSHIBE1, Katsuhiko MIWA1, Hidetoshi TERADA2, Yuji KATSUYAMA2
1

Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical
Company Limited, 2Life Science Business Department, Analytical & Measurement Instruments Division,
Shimadzu Corporation

An automated decision-making process enabling seamless transitioning from analytical to preparative
scale has been developed in collaboration with Shimadzu to improve puriﬁcation process by ReversedPhase High-Performance Liquid Chromatography-Mass Spectrometry (RP-HPLC-MS). Our method
scouting protocol is based on database mining of alternative conditions to identify proﬁtable separation
conditions, like acidic or neutral mobile phases. An intelligent data processing software, in particular“MS spectral purity” significantly improves accuracy of decision-making. This innovative system,

named “ASAPrepTM (Automated Scale-up from Analytical to Preparative)” has just been released
globally in August 2014 from Shimadzu.
In this poster presentation, we will show the advantages of this system, while highlighting the noveltyof the puriﬁcation procedures compared to the existing technology.

26G-ISMS20 Discovery of a Novel PDE10A Inhibitor as Highly Effective for Schizophrenia○ Yoichi KADOH1, Takehiko MATSUMURA1, Yoshihito TANAKA1, Mitsuya HONGU1,
Haruko MIYOSHI1, Mayumi KIMURA1, Kei TAKEDOMI1, Kenji OMORI1, Jun KOTERA1,Takashi SASAKI1, Kiichi TANAKA1, Keiko MIWA1, Tamaki KOBAYASHI1,
Hiroyuki TANIGUCHI1, Taketoshi ISHII1, Yumi WATANABE1, Haruna ITODA1,
Rikiya OHASHI1, Kouki KOJIMA1, Masaya FUKUDA1, Saori SATO1, Itsuko NAKAMURA1,
Toshiaki SAKAMOTO1, Toshiyuki HIMIYAMA1, Masataka HIKOTA1, Eiji KAWANISHI1
1

Mitsubishi Tanabe Pharma Corporation

Phosphodiesterase10A (PDE10A), a dual hydrolase of cAMP and cGMP, is highly expressed in striatal
medium spiny neurons (MSN). Inhibition of PDE10A modulates the activity of MSN via the regulationof cAMP. Therefore PDE10A inhibitor is expected as a therapeutic method for schizophrenia. We
transformed Avanafil 1 (PDE5 inhibitor) derivatives, and discovered compound 2 that had weak
inhibitory activity against PDE10A. More conversion of compound 2 improved the metabolic stability
and brain penetration, and dimethylaminoquinoxaline substituted compound 3 that attenuatedconditioned avoidance responses (CAR) in rats was produced. We performed in-depth optimization,and successfully obtained stilbene compound 4. The compound was substituted with 3-methyl-7-ﬂuoro
quinoxaline substituents, and reduced genotoxicity and CYP inhibition.

– 35 –

26G-ISMS21 Nucleic Acid Drugs Large Scale Manufacturing and Speciﬁcation

Assay– Equivalency Solid Phase versus AJIPHASE® and Oligonucleotide
Sequences Conﬁrmation for IND and NDA○ Satoshi INOUE1, Hirokazu NANKAI1, Emi SAITO1, Hideaki SATO1, Kazuhiko YUYAMA1
1

GeneDesign, Inc.

Oligonucleotides which constitutes nucleic acid drug, are provided by chemical synthesis. We
already have several track records of the GMP production of some nucleic acid drugs. All thesebatches were synthesized by solid phase synthesis which is well established organic chemistry but it islimited for scalability and cost effectivity. To overcome this issue, we have been co-developed liquid
phase synthetic methodology of oligonucleotides called AJIPHASE® originated by AJINOMOTO.
Comparison data between solid phase and AJIPHASE® showed that two methods are equivalent for
impurity proﬁle and purity. This result shows one of breakthrough of cost effective nucleic acid drug
development. We believe nucleic acid drugs development is accelerated by AJIPHASE®.
On the other hand, in the analysis of nucleic acid drugs for specification, sequence confirmation
examination is critical test of identiﬁcation. We show example of sequence conﬁrmation examination
using MS different methodologies.
We can cope to IND and NDA by above-mentioned production technology and analysis technique.

26G-ISMS22 Amycolamicin, a Novel Antibiotic as a Promising Candidate for

Clostridium Difﬁcile Infection: Antibacterial Activity, Mode of Action, andIn Vivo Efﬁcacy○ Yoshimasa ISHIZAKI1, Kazushige SASAKI1, Hideki HASHIZUME1, Chigusa HAYASHI1,

Kunio INOUE1, Hayamitsu ADACHI1, Yoshiaki TAKAHASHI1, Masayuki IGARASHI1,
Yoshio NISHIMURA1, Yuzuru AKAMATSU1, Akio NOMOTO1, Masakatsu SHIBASAKI1
1

Institute of Microbial Chemistry (BIKAKEN)

A novel antibiotic amycolamicin (AM) discovered from the culture broth of Amycolatopsis sp. MK575fF5 was originally isolated as a drug which showed strong antibacterial activities against Gram-positivebacteria such as MRSA, VRE and PRSP. Mode of action study revealed that AM inhibited bacterial
DNA gyrase with IC50 of 24.4 ng/ml, without cross-resistance to other inhibitors of DNA gyrase such asquinolones and aminocoumarins. By contrast, AM did not inhibit human DNA topoisomerase II.
Additionally, AM showed particularly strong antibacterial activity against C. difficile grownanaerobically. The MIC90s (n=45) of AM, vancomycin, and fidaxomicin were 0.25, 1.0, 0.25 µg/ml,
respectively. AM also showed strong antibacterial activity against 13 species of Clostridiales , some
Bacteroidales and Enterococcus faecalis/faecium , whereas showed moderate or weak antibacterial
activity against other enteric bacteria including Bifidobacteriales , Lactobacillales and some
Bacteroidales . In a therapeutic experiment using for antibiotic- associated pseudomembranous colitis
caused by C. difficile ATCC 43255 in hamsters, AM showed an equivalent therapeutic efficacy toﬁdaxomicin at 6, 20, and 60 mg/kg/day by oral administration (n=7).
In conclusion, AM showed to possess strong activity against C. difficile with novel mechanism ofaction. The efﬁcacy in hamster model for pseudomembranous colitis warrants further evaluation of AM.
– 36 –

26G-ISMS23 Identiﬁcation and Optimization of a Novel Series of Tetrahydroisoquinoline

Derivatives as an Orally Active MGAT2 Inhibitor○ Tsuyoshi BUSUJIMA1, Hiroaki TANAKA2, Eiji MUNETOMO3, Kiyokazu KITANO3,

Masako SAITO3
1
3

Pharamceutical Science Laboratories, 2Chemistry Laboratories,
Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.

MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug
treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity
relationship (SAR) study of 2,3-dihydro-1H -isoindole-5-sulfonamide derivatives which was derived
from a hit compound identiﬁed by our high throughput screening campaign. In this study, we identiﬁed
an orally available MGAT2 inhibitor through optimization in terms of solubility. This compound
exhibited moderate potency in the enzyme inhibitory assay (IC50 = 1522 nM) and an in vivo efﬁcacy atan oral dose of 100 mg/kg in a mouse oral lipid tolerance test.
Further optimization of a novel series of 1,2,3,4-tetrahydroisoquinoline-6-sulfonamide derivatives toimprove the intrinsic potency culminated in the identiﬁcation of TP0455353, 2-[2-(4-tert -butylphenyl)
ethyl]-N -[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroiso-quinoline-6-sulfonamide,
which was the most potent MGAT2 inhibitor among this series with an IC50 value of 28 nM. Oraladministration of TP0455353 at a dose of 3 mg/kg in the oral lipid tolerance test resulted in signiﬁcant
suppression of triglyceride synthesis.

26G-ISMS24 Discovery of Novel Fluoroquinolone Antibiotics WFQ-101 and

Its Optimization Study○ Tatsuya HIRANO1, Tomohiko KINOSHITA1, Daichi KAZAMORI1, Satoshi INOUE1,

Kouji NISHIMURA1, Asuka SAKURAI1, Ayuka SASAKI1, Yasuhiro KURAMOTO1,
Hirotaka AMANO1, Akira YAZAKI1
1

Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd.

As the difﬁcult-to-treat infections caused by multidrug-resistant bacteria have spread, it is an urgent
need to develop novel antibiotics for the treatment of them. Therefore, we started the research todiscover novel antibiotics with potent antibacterial activities, especially against Gram-negative resistantpathogens.
Recently, we evaluated the minimum inhibitory concentration (MIC) of our quinolone library for

P. aeruginosa with or without the efﬂux pump inhibitor PAβN. We found that the MICs of a certain
type of compounds such as WFQ-101, having 2-hydroxymethylphenyl group at 1-position, wereless changed by the presence of PAβN, indicating the possibility to overcome the drug resistance bybacterial efﬂux system. We selected WFQ-101 as a lead compound and have continued its structural
optimization. For example, an introduction of 5-methyl group drastically increased the activity,
whereas the modiﬁcation of 7-substituent, such as the increases of lipophilicity and/or bulkiness, was
not tolerated for the activity against Gram-negative pathogens. In this presentation, we will describe theresults of our optimization study, demonstrating the Structure-Activity Relationship.

– 37 –

26G-ISMS25 Anti-CTLA-4 Antibody scFv Producing Recombinant Biﬁdobacterium

Secretes CTLA-4 Blocker Speciﬁcally Inside Hypoxic Tumor and Suppresses
Tumor Growth in Syngeneic Mice Model○ Shiro KATAOKA1, Koichiro SHIOYA1, Li WANG1, Tomio MATSUMURA1,

Hitomi SHIMIZU1, Yasuyoshi KANARI1, Yuji SEKI1, Yuko SHIMATANI1,
Minoru FUJIMORI2, Shunʼichiro TANIGUCHI3
1

Anaeropharma Science, Inc., 19-8, Nihonbashi Kabuto-cho, Chuo-ku, Tokyo 103-0026, Japan,
Department of Breast Surgery, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan,
3
Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine
2Anti-PD-1 antibody and anti-CTLA-4 antibody showed notable efficacy and the combination
complimentarily enhanced antitumor beneﬁt. Nevertheless, either single-agent therapy or combination
therapy is facing immune-related adverse events (irAEs), which are major cause of treatment
discontinuation. Non-speciﬁc systemic activation of normal immune system by the therapy is one ofmajor reasons to cause the problems. Approaches to increase the delivery of checkpoint blockers totumor site may minimize the irAEs and improve the response rate in patients.
In an aim to improve efﬁciency of anti-cancer drug delivery, we have been developing in situ Delivery
and Production System (i -DPS) by modifying a non-pathogenic anaerobic bacterium, Biﬁdobacterium ,which localizes and proliferates only in the hypoxic environment like solid tumors after I.V.
administration and also produces anticancer proteins, enzymes or other pharmacologically active
molecules selectively at the tumor site. Here we present anti-CTLA-4 antibody scFv producing i- DPS
in cancer immunotherapy, which could be speciﬁcally delivered to and ampliﬁed only at the hypoxic
sites of solid tumors.

26G-ISMS26 Structural Basis for Activation of Neisseria Meningitides Elongation Factor

P with Arginine-32 Rhamnosylation by EarP
○ Toru SENGOKU1
1

RIKEN Structural Biology Laboratory

Protein glycosylation is a universal post-translational modiﬁcation regulating many cellular processes.
The only known protein arginine rhamnosyltransferase, EarP, specifically rhamnosylates Arg32
of elongation factor P (EF-P). We report a crystallographic study of Neisseria meningitidis EarP.
EarP binds the entire beta-sheet structure of domain I of EF-P, forming numerous interactions thatspeciﬁcally recognize its conserved sequences. This recognition mechanism, which is both structureand sequence-specific, sharply contrasts with those of other known glycosyltransferases that accept
substrates with different sizes and/or sequences. A molecular dynamics simulation suggested that therhamnose moiety should change its conformation during the reaction. These insights should facilitate
the development of new EarP inhibitors that target only EarP-containing pathogenic bacteria.

– 38 –

26G-ISMS27 Design, Synthesis and Biological Evaluation of a Novel Series ofPeripheral-selective Noradrenaline Reuptake Inhibitor, Part I -Lead Series
Discovery and Biological Concept Validation○ Ikuo FUJIMORI1, Tomoya YUKAWA1, Taku KAMEI1, Yoshihisa NAKADA1,

Nobuki SAKAUCHI1, Masami YAMADA1, Yusuke OHBA1, Maiko TAKIGUCHI1,
Masako KUNO1, Izumi KAMO1, Hideyuki NAKAGAWA1, Teruki HAMADA1, Tomoko
IGARI1, Teruaki OKUDA1, Satoshi YAMAMOTO1, Tetsuya TSUKAMOTO1, Yuji ISHICHI1,
Hiroyuki UENO1
1

Takeda Pharmaceutical Company Limited

Centrally acting noradrenaline reuptake inhibitor (NRI) is reportedly effective for patients withstress urinary incontinence (SUI) by increasing urethral closure in the clinical Phase IIa study
with esreboxetine. Noradrenaline transporters are expressed in both central and peripheral nervous
systems and the contribution of each site to efficacy has not been clarified. This poster describes
the development of a series of peripheral-selective 7-phenyl-1,4-oxazepane NRIs to investigate thecontribution of the peripheral site to increasing urethral resistance in rats. An acetamide derivative
which showed high peripheral NET selectivity in rats increased urethral resistance in a dose-dependent
manner and exhibited a maximal effect on par with esreboxetine. These results indicate that theurethral resistance-increasing effects of NRI in rats are fully achieved by the peripheral selective NET
inhibition.

26G-ISMS28 Design, Synthesis and Biological Evaluation of a Novel Series ofPeripheral-selective Noradrenaline Reuptake Inhibitor, Part II -Lead
Optimization with Avoiding P-gp Substrate and Genetic Polymorphism○ Tomoya YUKAWA1, Ikuo FUJIMORI1, Taku KAMEI1, Yoshihisa NAKADA1,

Nobuki SAKAUCHI1, Masami YAMADA1, Yusuke OHBA1, Hiroyuki UENO1,
Maiko TAKIGUCHI1, Masako KUNO1, Izumi KAMO1, Hideyuki NAKAGAWA1,
Yasushi FUJIOKA1, Tomoko IGARI1, Yuji ISHICHI1, Tetsuya TSUKAMOTO1
1

Takeda Pharmaceutical Company Limited

Peripherally selective inhibition of noradrenaline reuptake is a novel mechanism for the treatmentof stress urinary incontinence to overcome adverse effects associated with central action. Herein, we
describe our medicinal chemistry approach to discover peripheral-selective noradrenaline reuptake
inhibitors to avert the risk of P-gp-mediated DDI at the blood–brain barrier. We observed that stericshielding of the HBA and HBD reduced the multidrug resistance protein 1 (MDR1) efflux ratio;
however, the resulting compound was mainly metabolized by CYP2D6 and CYP2C19 in the invitro phenotyping study, implying the risk of PK variability based on the genetic polymorphism.
Replacement of the hydrogen atom with a deuterium atom in a strategic, metabolically hot spot led tocompound, which was mainly metabolized by CYP3A4. To our knowledge, this study represents theﬁrst report of the effect of deuterium replacement for a major metabolic enzyme.

– 39 –

26G-ISMS29 Ex Vivo Gene-manipulated Mature Adipocytes: Novel Gene Therapy Medicine

for Sustained Protein Replacement Therapy of Variety of Intractable Diseases○ Masayuki KURODA1, Hideaki BUJO2, Koutaro YOKOTE3, Yasushi SAITO4, Masayuki ASO5
1

Center for Advanced Medicine, Chiba University, 2Department of Clinical Laboratory Medicine, Toho
University Medical Center Sakura Hospital, 3Department of Clinical Cell Biology and Medicine, Graduate
School of Medicine, Chiba University, 4Superintendent of the hospital bureau, City Hall of Chiba,
5CellGenTech, Inc.

Gene therapy-based protein replacement is one of absolute needs for treatment of inherited diseases.
Based on much experiences of clinical transplantation therapy in cosmetic and reconstructive surgery,adipose tissue is now recognized as a source of proliferative cells for cell-based therapy. We havedeveloped manipulation procedure of mature adipocytes through ceiling culture with subsequent
retroviral/lentiviral gene transduction. The propagated cells, designated as ceiling culture-derived
proliferative adipocytes (ccdPAs), provide efﬁcient gene transduction efﬁciency with stable secretion of
the transduced-gene products. GMP production procedure, by which the gene-transduced ccdPAs could
be expanded up to nearly 1012 cells from 1 g of fat tissue for three weeks after fat tissue preparation,
has been developed. The platform technology has been applied for ex vivo gene therapy of familial
lecithin:cholesterol acyltransferase (LCAT) deﬁciency. Clinical ﬁrst in human study for treatment offamilial LCAT deﬁciency has been approved by Ministry of Health, Labour and Welfare, followed byinitiation of patient enrollment in Japan. We further continue our research and development to obtainapproval as gene therapy medicine. Thus, ccdPAs would provide an excellent platform for developing
a protein replacement therapy not only for LCAT deficiency but also variety of intractable diseases
including hemophilia and lysosomal storage diseases.

26G-ISMS30 Application of Novel Highly Immunodeﬁcient Mice for Patient Derived Xenograft(PDX) Model and Evaluation of Anticancer Therapy○ Seiji OKADA1, Kulthida VAETEEWOOTTACAHRN1, Hiroki GOTO1, Ryusho KARIYA1
1

Center for AIDS Research and Graduate School of Medical Sciences, Kumamoto University

Xenograft tumor models from patient-derived tumor tissue at low passage have been shown toconserve original tumor characteristics such as heterogeneous histology, clinical biomolecularsignature, malignant phenotypes and genotypes, tumor architecture and tumor vasculature. Patientderived tumor xenografts (PDX) are now believed to offer relevant predictive insights into clinicaloutcomes when evaluating the efﬁcacy of novel cancer therapies. NOD/Scid based immunodeﬁcient
mice (ex. NOD/Scid, NOG, NSG, and NOJ mice) have been used as the recipient of human tumortransplantation due to the high forming efficiency, however, these mice are relatively weak, shorter
life span and low breeding efﬁciency. We developed Balb/c Rag-1 Jak3 double deﬁcient (Balb/c RJ)
mice to cover these disadvantages. Breeding efficiency of Balb/c RJ mice are same as Balb/c miceand human hematopoietic cells and tumor cells are also successfully seeded and developed in Balb/c RJ mice. We transplanted patient derived cholangiocarcinoma (CCA) tissue into Balb/c RJ mice
subcutaneously, and 16 out of 20 cases formed tumors in mice, and 4 CCA cell lines were establishedfrom PDX tissue culture.
PDX model using Balb/c RJ mice can be the useful tool for cancer research and drug development.

– 40 –

26G-ISMS31 The Unbound Concentration of Multimodal Drugs in the Assay Medium Usedin the Multi-electrode Array System for Cardiac Risk Assessment with iPS Cellderived Cardiomyocytes○ Takashi YOSHINAGA1,4, Raku SINKYO2, Kiyomi KIKUCHI2, Tomohiko TANIGUCHI1,4,

Yuko SEKINO3,4, Kohei SAWADA1,4
1

Global CV Assessment, Eisai Co., Ltd., 2Global DMPK, Eisai Co., Ltd., 3Division of Pharmacology, National
Institute of Health Sciences, 4Japan iPS Cardiac Safety Assessment (JiCSA)

To characterize and predict the QT interval prolongation and proarrhythmia potential of drug candidates,
investigations into the challenges of using multi-electrode array system and human stem cell-derived
cardiomyocytes are on-going. Sometimes, discussions arise on whether assay results should beinterpreted using total (applied) or unbound concentrations to understand the compounds cardiovascularliabilities. To provide useful suggestions, we measured the unbound concentrations of 59 drugs which
include CiPA selected 29 compounds in the iCell Cardiomyocytes Maintenance Medium (CMM,
Cellular Dynamics International) including fetal bovine serum by equilibrium dialysis method using
Rapid Equilibrium Dialysis device (ThermoFisher Scientiﬁc). Then, unbound fraction (fu) values at low
and high concentrations (100-fold differences) in CMM were calculated. When saturation of bindingat the high concentration was observed, an additional experiment was done at a middle concentration.
Most of compounds showed similar fu values at low and high concentrations. On the other hand, several
compounds such as Mibefradil, Thioridazine, Bepridil, Prenylamine, Tolterodine, Haloperidol, andDronedarone showed more than 2-fold higher fu values at high concentrations than those at low ones.
Tamoxifene and Amiodarone showed very low fu values (less than 0.01) which indicated very strong
protein binding. Further analysis of the relationships between the fu values in CMM and human plasma
was conducted. Good correlation in rank order with non-linier correlation was obtained. These results
indicated that the actual unbound concentrations in CMM will be very useful to consider and interpretthe relationship to unbound plasma concentrations which caused CV events in human.

26G-ISMS32 Discovery of ASP3026, a Potent and Selective Anaplastic Lymphoma Kinase(ALK) Inhibitor○ Kazuhiko IIKUBO1, Yutaka KONDOH1, Itsuro SHIMADA1, Takahiro MATSUYA1,

Kenichi MORI1, Yoko UENO1, Sadao KUROMITSU1, Minoru OKADA1
1

Astellas Pharma Inc.

Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancers,
including echinoderm microtubule-associated protein-like 4 (EML4)-ALK positive non-small celllung cancer. We synthesized a series of 1,3,5-triazine derivatives and discovered ASP3026 as apotent and selective ALK inhibitor, which demonstrated dose-dependent antitumor activity in micebearing NCI-H2228 tumor xenografts. ASP3026 also showed inhibitory activity against the L1196M
gatekeeper mutant of ALK. Syntheses and structure-activity relationships of 1,3,5-triazine derivatives
and computational modelings of ASP3026 will be presented.

– 41 –

26G-ISMS33 Immune Proﬁling with a New NGS-based Repertoire Analysis○ Takaji MATSUTANI1, Kazutaka KITAURA1, Hiroshi YAMASHITA1, Hitomi AYABE1,
Hiroyuki SATO1, Yuichi MORITA1, Tadasu SHINI2,3, Ryuji SUZUKI1,3
1

Repertoire Genesis Incorporation, 2BITS. Co., Ltd., 3Clinical Research Center for Rheumatology and Allergy,
Sagamihara National Hospital

NGS-based TCR and BCR repertoire analyses are powerful tools to analyze speciﬁcities and diversities
of T and B cells. Here, we developed a new TCR/BCR repertoire analysis methods using unbiased
ampliﬁcation (adaptor-ligation PCR) and an in-house developed analysis software following a pairedend MiSeq sequencing. This method enables a highly accurate and quantitative analysis. With regard
to TCR, we examined gene usage, diversity and similarity of TRA/TRB repertoires with PBMCs of
20 healthy individuals. TRA repertoires were more similar between individuals than TRB repertoires
were. The inter-individual similarity of TRA depended largely on the frequent presence of shared TCRs
among two or more individuals. The shared TRA sequences often contained invariant TCRα derived
from invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells. Regarding
BCR, we sequenced ﬁve isotypes of IgH (IgM, IgD, IgG, IgA and IgE) in 12 individuals and analyzed
frequencies of somatic hypermutation (SHM) among Ig subclasses. Shared sequences were frequently
observed within multiple Ig subclasses and the frequency of SHM varied among the Ig subclasses.
Respite the sequential class-switch recombination (CSR) from upstream to downstream subclasses, theshared clones had the almost same SHM levels while subclass-speciﬁc clones had a different levels of
SHM dependent of genomic location. These results gave us an interesting insight into the development
and the maturation of B cells. In conclusion, NGS-based TCR/BCR repertoire analysis will provide us
critical information on T and B cells playing a pivotal role in immune system.

26G-ISMS34 Cyclodextrin-based Supramolecular Drug Carriers and Active Pharmaceutical

Ingredients○ Taishi HIGASHI1, Keiichi MOTOYAMA1, Hidetoshi ARIMA1,2
1

Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University,
Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented)
Program”, Kumamoto University
2

Cyclodextrins (CyDs) are cyclic oligosaccharides composed of six (α-CyD), seven (β-CyD), and eight(γ-CyD) glucopyranose units that can form inclusion complexes with various organic and inorganic
compounds. Recently, we have developed CyD-based supramolecular drug carriers for low-molecularweight drugs, peptide/protein drugs, gene and nucleic acid drugs through the combination withfunctional polymers or macromolecules, such as dendrimer, polyethylene glycol (PEG) and liposome(Fig. 1). Moreover, we also utilized CyDs as active pharmaceutical ingredients. In this presentation,
we introduce the recent applications of CyDs as drug carriers
and active pharmaceutical ingredients. The topics of thepresentation are shown as follows.
1) Folate-appended CyDs as drug carriers for low-molecularweight anticancer drugs
2) Reversible PEGylation for peptide/protein drugs based on
CyD/adamantane interaction3) Polypseudorotaxane hydrogels as a stabilizer for antibodies
4) Ligand-appended dendrimer/CyD conjugates as gene andnucleic acid drugs carriers5) Folate-appended CyDs as tumor-selective anticancer drugs– 42 –

26G-ISMS35 Antifungal Activities and Nonclinical Pharmacokinetics of APX001A/APX001(E1210/E1211), a New Broad-Spectrum Antifungal, with a New Mode of Action○ Takaaki HORII1
1

Global Health Research Section, hhc Data Creation Center, Eisai Co., Ltd.

APX001A (formerly known as E1210) inhibited the inositol acylation of fungus-specificglycosylphosphatidylinositol (GPI), which is catalyzed by Gwt1p, leading to the inhibition of GPIanchored protein maturation. The compound not only inhibited fungal growth, but also suppressed
the expression of some virulence factors of fungi. APX001A demonstrated potent, broad-spectrum
antifungal activity against clinically important fungi, including Candida spp., Aspergillus spp., andother filamentous fungi. It showed no cross-resistance with azoles and echinocandins. APX001(formerly known as E1211) is a water-soluble prodrug of APX001A, and efficiently converted to
APX001A in animals, and in human S9 tissue fractions in vitro. APX001 was effective in murine
models of candidiasis, aspergillosis, fusariosis, and scedosporiosis. Furthermore, APX001/ APX001A
demonstrated synergy in combination with other antifungals in vitro and in vivo against Candida spp.
and Aspergillus spp. Amplyx Pharmaceuticals was licensed E1211 and E1210 from Eisai in 2015, andrenamed APX001 and APX001A, respectively. Amplyx is now advancing the evaluation of APX001 in
Phase 1 program using both IV and oral formulations to address the need for hospital administration, as
well as continued dosage after hospital discharge. Amplyx plans to initiate Phase 2 studies in 2017.

26G-ISMS36 Synthesis and Evaluation of Potent, Orally Available, Well-balanced EP2 andEP3 Dual Agonists○ Akihiro KINOSHITA1, Masato HIGASHINO1, Koji YOSHIDA1, Yoshiyuki ARATANI1,

Akito KAKUUCHI1, Keisuke HANADA1, Hiroyuki TAKEDA1, Toshikiko NISHIYAMA1,
Hidekazu MATSUYA1, Kazuyuki OHMOTO1
1

Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd.

Our purpose was to develop PGE2 analogs possessing highly potent dual EP2 and EP3 agonist
activity with selectivity against the other two subtypes (EP1 and EP4), because a dual EP2 and EP3
agonist is expected as an effective therapeutics addressing unmet medical needs for treatment of aunderactive bladder (UAB). While no dual EP2 and EP3 agonist has been reported, a dual EP2 and EP4
agonist with selectivity against the EP1 and EP3 receptor subtypes was reported in 20121. At ﬁrst, we
synthesized cyclic carbamate derivatives having cyclobutyl group and terminal ﬂuorine atom in orderto reduce EP4 agonist activity and add EP3 agonist activity, and then replaced the core structure withcyclopentanone for enhancement of orally absorption. The resulting compound, ONO-8055, showed
excellent potency (human EC50 EP2 = 0.67 nM，EP3 = 0.7 nM), EP1 and EP4 subtype selectivity(>400-fold) and good pharmacokinetic proﬁles. Regarding in vivo efﬁcacy, ONO-8055 improved thelower urinary tract dysfunctions of neurogenic underactive bladder in a rat lumber spinal stenosis (LCS)
model2. Furthermore, as a result of Phase I trial in Europe, there was no safety or PK concern. ONO8055 is currently under development as a new highly promising UAB drug.
1)
Kambe, T.; Maruyama, T; Nakai, Y; Oida H.; Maruyama T.; Abe N.; Nishiura, A.; Nakai, H.; Toda, M.
Bioorganic & Medicinal Chemistry , 2012, 20 , 3502.
2)
Sekido N.; Kida J.; Mashimo H.; Wakamatsu D.; Okada H.; Matsuya H.; J Urol, 2016, 196 , 609.
– 43 –

26G-ISMS37 Novel Development of Chemotherapy for Relapsed and Refractory AML Basedon the Promising Functional Mechanism of Cytidine Analog, DFP-10917○ Masakazu FUKUSHIMA1, Kenzo IIZUKA1, Chung ZHANG1, Cheng JIN1,

Kiyoshi ESHIMA1
1

Division of Research and Development, Delta-Fly Pharma, Inc.

Acute myeloid leukemia (AML) is still progressed disease vigorously challenging to urgently improvea prognosis in patients. At present time, induction-chemotherapy with cytarabine (one of cytidine
analog) combined with anthracycline drugs has been frequently conducted for the treatment of AML,
and sequential consolidation-chemotherapy with almost same regimen is performed for patients.
However there are few suitable treatment options for patients with relapsed and refractory AML.
We developed a new generation of cytidine-type antitumor nucleoside, DFP-10917 and investigated
the antitumor efﬁcacy and functional mechanism of this drug in vitro and in vivo using human tumor
cells. DFP-10917 showed the most potent antitumor activity on tumor models in mice following its
prolonged (14-days) infusion at very low-dose (4.5 mg/kg/day) compared to short injection of DFP10917 and of other cytidine analog. Under such prolonged dosing schedule, DFP-10917 is converted toits nucleotide form and subsequently incorporated into DNA in tumor cells which cause DNA-strand
breaks resulting in G2/M phase-arrest by cellular checkpoint regulators and resultantly formed theultimate apoptotic cells. In contrast, cytarabine is converted to their nucleoside-triphosphates and theninhibit DNA polymerase activity leading to protection of DNA biosynthesis during the S-phase of thecell cycle.
To evaluate clinical efﬁcacy and toxicity in phase I/II study of DFP-10917, AML patients were treated with
continuous infusion (CI) of DFP-10917. In phase I study, low-dose (6 mg/m2) 14-day CI of DFP-10917
was found to result in a clinical beneﬁt to patients as recommended dose and schedules. In phase II study,
total 29 patients were enrolled and the response rate and the median survival time in relapsed/refractory
AML patients were 48% and 7.3 months, respectively. No patients discontinued DFP-10917 treatment due
to unacceptable drug-related toxicity. Further study of DFP-10917 in a phase III study in AML is planned.

26G-ISMS38 System-wide Temporal Characterization of the Phosphoproteome ofNon-small-cell Lung Cancer Cells Treated with Erlotinib○ Adachi JUN1, Yuichi ABE1, Maiko SHIMIZU1, Marina KISHIDA1, Ayako SATO1,

Takeshi TOMONAGA1
1

Laboratory of Proteome Research National Institutes of Biomedical Innovation, Health and Nutrition

Phosphoproteome is one of key signatures to understand the mode of action and mechanism of drug
resistance of kinase inhibitors at the molecular level, pathway level and system level. We developed
sensitive and high-throughput phosphoproteome and tyrosine phosphoproteome analysis platform andperformed temporal characterization of non-small-cell lung cancer cell lines treated with erlotinib.
We obtained phosphoproteome and phosphotyrosine-proteome proﬁles of two erlotinib-sensitive cells
and four erlotinib-resistant cells treated by erlotinib for 0 h, 6 h and 24 h. We quantiﬁed over 12000
phosphorylation sites by phosphoproteome analysis and over 600 phosphorylation sites on tyrosine
residue by phosphotyrosine-proteome.
We extracted kinases and other enzymes which are up-regulated in resistant cells and selected 46
inhibitors for drug screening. 24 of 46 inhibitors inhibited cell growth of at least one resistant cell line.
Our sensitive and high-throughput phosphoproteome and tyrosine phosphoproteome analysis platform
has a potential to identify pharmacoproteomic markers of drug efficacy as well as candiates ofmolecular targets to overcome drug resistance.

– 44 –

26G-ISMS39 Identiﬁcation of WAC-224, a Novel Anticancer Quinolone as a Human

Topoisomerase II Inhibitor○ Tomonori YAMAGUCHI1, Kenji ITOH1, Taichi UESHIMA1, Rumiko SHIMABARA1,

Yohei KAWAKUBO1, Masayuki SATO1, Junpei YAMASHITA1, Tatsuya HIRANO1,
Akira YAZAKI1
1

Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd.

Topoisomerese II inhibitors, such as Anthracyclines, are an important class of chemotherapeutic
agents, which are employed for the treatment in multiple types of cancers including acute myeloid
leukemia (AML). However, the therapeutic applications of Anthracyclines are limited because ofa cumulative cardiotoxicity and an efflux-mediated drug resistance. WAC-224 is a novel anticancer
quinolone derivative targeting human topoisomerase II and has the superior characteristics in potency
and safety both in vitro and in vivo compared with Vosaroxin (QINPREZO®, formerly SNS-595),
which showed lower potential for cardiotoxicity in the clinical trials. In our evaluations, WAC-224 hadhigher selectivity for cancer cells versus normal cells in its antiproliferative activity; the IC50 value was
1.4 nM for MV4-11 AML cell line versus > 50 μM for MRC-5 normal cell line. WAC-224 also showed
the potent in vitro activity against multi drug-resistant cell lines such as MES-SA/Dx-5. Additionally,in vivo murine xenograft studies conﬁrmed the potent therapeutic effects of WAC-224 for therapy ofdifferent types of cancers including multi-drug resistant one. These results suggest that WAC-224 is apotentially effective therapeutic agent for leukemia and multi-drug resistant cancers.

26G-ISMS40 Lenvatinib Mesilate (LEN) Enhanced Antitumor Activity of a PD-1 Blockade

Agent by Potentiating Th1 Immune Response○ Yu KATO1, Xingfeng BAO2, Shannon MACGRATH2, Kimiyo TABATA1, Yusaku HORI1,

Sho TACHINO1, Mark MATIJEVICI2, Yasuhiro FUNAHASHI1, Junji MATSUI1
1

Eisai Co., Ltd., Tsukuba, Ibaraki, Japan, 2Eisai Inc. Andover, MA, USA

Lenvatinib (LEN) selectively inhibits the kinase activities of VEGFR1-3, FGFR1-4, KIT, PDGFRα,and RET, which are involved in tumor angiogenesis and tumor cell proliferation in several cancer types.
Currently, Phase 1b/2 clinical trials of the combination of LEN and pembrolizumab (a monoclonal
antibody [mAb] that blocks the interaction between PD-1 and its ligands) are ongoing for selected
types of cancer including renal cell carcinoma, melanoma and non-small cell lung carcinoma, etc.
In this study, we will report that tumor associated macrophage and regulatory T cell population were
downregulated by treatment of LEN, and combination of LEN with PD-1 mAb showed more potent
antitumor activity in CT26 mice tumor syngenic model compared with either single treatment alone.
Notably, complete tumor regressions were detected in some mice with combination treatment in the
H22 mice tumor syngenic model. Re-inoculation of fresh H22 cells into these cured mice was rejected.
BioMap analysis showed that PD-1 mAb increased both Th1 and Th2 cytokines, LEN decreased Th2
cytokines, and combination treatment increased Th1 cytokines but decreased Th2 cytokines.
The results indicate that the combination of LEN with PD-1 mAb was more effective than single-agent
treatment in multiple syngeneic tumor models and was accompanied with a potent antitumor immune
response.
– 45 –

26G-ISMS41 Identiﬁcation of Blood-based Gene Expression Biomarkers for Major Depressive

and Bipolar Disorders○ Seiji NAKAMURA1, Hiroaki HORI2, Yohei ISHIZAWA1, Kenichi MATSUBARA1,

Ryo MATOBA1, Hiroshi KUNUGI2
1

DNA Chip Research Inc., 2Department of Mental Disorder Research, National Institute of Neuroscience,
National Center of Neurology and Psychiatry

Major depressive and bipolar disorders are typical psychiatric problems affecting about 350 million
people globally. Pathogenesis is not fully understood and laboratory tests for diagnosis and prognosis
are not established. We have performed microarray analysis using blood samples of major depressive
and bipolar disorder (n=25) patients against age, gender-matched healthy controls (n=25). Genes related
to ribosomes were found to be up-regulated in patients of major depressive and bipolar disorders.
Ribosomal proteins RPL17 and RPL34 were further validated by qRT-PCR using independent test
cohorts (15 patients each for depressive and bipolar against healthy controls). Reproducibility of theresult indicates that ribosomes related genes could serve as useful screening biomarkers.

26G-ISMS42 Anti-Helicobacter Pylori Activity of a Novel Derivative of Intervenolin○ Tomokazu OHISHI1, Toru MASUDA1, Shun-ichi OHBA1, Chigusa HAYASHI2,
Hikaru ABE3, Masayuki IGARASHI2, Takumi WATANABE3 , Daniel Ken INAOKA4, Kiyoshi
KITA5, Masakatsu SHIBASAKI3, Manabu KAWADA1,6
1

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation,
Institute of Microbial Chemistry (BIKAKEN), Laboratory of Microbiology, Microbial Chemistry Research
Foundation, 3Institute of Microbial Chemistry (BIKAKEN), Laboratory of Synthetic Organic Chemistry,
Microbial Chemistry Research Foundation, 4Center for International Collaborative Research, Nagasaki
University, 5School of Tropical Medicine and Global Health, Nagasaki University, 6Institute of Microbial
Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation
2

Colonization and infection of Helicobacter pylori (H. pylori ) is a major cause of gastric diseases including
gastritis, peptic ulcers, and gastric cancer. Therefore, eradication of H. pylori leads to prevention of gastricdiseases. Although standard treatment for H. pylori involves a combination of antibiotics, they kill mostbacteria in our body, leading to the occurrence of side effects. We previously found that an antitumor
agent intervenolin (ITV) also exhibits selective anti-H. pylori activity. Here we demonstrate that a novel
derivative of ITV showed selective anti-H. pylori activity like ITV without any effect on other bacteria
including intestinal bacteria. Interestingly, oral monotherapy of the ITV derivative had a stronger anti-

H. pylori activity without any side effects in a mouse H. pylori -infection model than that of ITV and thestandard triple therapy of a proton pump inhibitor and two antibiotics. These results suggest that the ITVderivative would be a new potential therapeutic agent for H. pylori infection treatment. Now, we aretrying to identify a molecular target of the ITV-derivative against H. pylori .

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26G-ISMS43 Discovery of Novel 5,6,7,8-tetrahydro[1,2,4]Triazolo[4,3-a ]Pyridine Derivatives asγ-secretase Modulators○ Takafumi TAKAI1, Tatsuki KOIKE1, Minoru NAKAMURA1, Yasutaka HOASHI1,
Yoshihide TOMATA1, Sachie MORIMOTO1, Yuichi KAJITA1, Toshiro YAMASHITA1,
Naohiro TAYA1, Tetsuya TSUKAMOTO1, Tomomichi WATANABE1, Koji MURAKAMI1,
Tomoko IGARI1, Makoto KAMATA1
1

Takeda Pharmaceutical Company Limited

γ-Secretase modulators (GSMs), which lower pathogenic amyloid beta (Aβ) without affecting the

production of total Aβ or Notch signal, have emerged as a potential therapeutic agent for Alzheimerʼs disease (AD). A novel series of 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a ]pyridine derivatives was
discovered and characterized as GSMs. The optimization study using ligand-lipophilicity efficiency(LLE) as a drug-likeness guideline led to identiﬁcation of various types of high-LLE GSMs with potent
in vivo Aβ42-lowering effects by single administration. Furthermore, multiple oral administration of
the representative compound signiﬁcantly reduced soluble and insoluble brain Aβ42, and ameliorated
cognitive deﬁcit in novel object recognition test (NORT) using Tg2576 mice as an AD model.

26G-ISMS44 Regulatory Science for R&D Promotion of Innovative Pharmaceuticals*
Kazuhiko MORI1, Takao YAMORI2, ○ Toru KAWANISHI3, Takao INOUE4
1

Ministry of Health, Labor and Welfare (MHLW), 2Pharmaceuticals and Medical Devices Agency (PMDA),
National Institute of Health Sciences (NIHS), 4Japan Agency Medical Research and Development (AMED)

3

At present the nation ʼ s policy for research and development (R&D) promotion of innovative
pharmaceuticals and improvement of environments for the R&D is formulated by Japanese
government. In the policy the enhancement and promotion of Regulatory Science (RS) touching theappropriate and rapid predict, evaluate, and judgment of quality, efﬁcacy and safety of pharmaceuticals
is especially stressed. Following the nationʼs policy, the MHLW is promoting the strategy package(Strategy of SAKIGAKE) facilitating all the process from R&D, clinical research/trials, pre- andpost- marketing safety, insurance coverage, through globalization of innovative products which are
to be put into practical use, targeting innovative pharmaceuticals which can cure serious illnesses. In
concert with the MHLW, the PMDA is building up the systems, such as priority consultations, priorassessment, and priority reviews. The PMDA is taking various approaches such as the introductionof data mining methods and safety evaluation of drugs based on pharmaco-epidemiological methods
utilizing electronic medical records, or construction of medical information database (MID-NET), toenhance and advance safety measures. The PMDA has also established the Science Board consistingof external experts to discuss the evaluation methods of innovative drugs. The pharmaceuticals-related
divisions in the NIHS have carried out RS research to develop the point-to-consider documents or
standardized methods for evaluating mainly quality and non-clinical safety of innovative products suchas nanomedicines, fully engineered protein drugs, oligonucleotide drugs, and so on. The AMED is
supporting about 80 research projects by the Grant Program naming “Research on Regulatory Scienceof Pharmaceuticals and Medical Devices”.
*The poster is presented by Division of Regulatory Science, Pharmaceutical Society of Japan.
– 47 –