Super-Curcumin Story
Chapter 1: Curcumin is excellent compound for various medicinal usages
Chapter 2: Discovery of Super-Curcumin analog
Chapter 3: Anti-tumor activities of Super-Curcumin analog
Chapter 4: Molecular targets of analogs
Chapter 5: Oncogenes & analogs
Chapter 6: Apoptosis & analogs
Chapter 7: Cancer stem cells & analogs
Chapter 8: Analogs lead drug discovery
Supplement: Super-Curcumin analog & Sleeping sickness (African trypanosomiasis)

Chapter 1: Curcumin is excellent compound for various medicinal usages

Curcumin

We can eat it!
IUPAC name; (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6- heptadiene-3,5-dione

Curcumin is a multi-targeted compound

Defeatall enemies ！

CurCurcumin can stop the individual gears of wheels in cancer.

Curcumin man

Why does curcumin have a multiplicity of targets?

Michael reaction
High affinity to proteins via a thiol groupProtein

How can curcumin control multiple targets? – “Resilience”‐
Pros

Conscurcumin

Well balanced
Healthy

Pros
Molar ratioConsEx)
Anti‐oncogene
Th1Cancer
Infection
Inflammation
Alzheimer
Tumor immune toleranceEx)Oncogene
Th2Resilience
Recovery of healthChapter 2: Discovery of Super-Curcumin analog

Collaborator;
Dept. Organic Chemistry,
Graduate School of Pharmaceutical Science
Tohoku Univ.
Analog screening was started
from the chemical librarystored in Dept., Organic Chem.

Chapter 3: Anti-tumor activities of Super-Curcumin analog
0> 50
16types of cancer cell lines

89 spiecies of analogs
Over 100 species of analogs were synthesized from one lead compound,and the anti-tumor activities against 16 types of cancer cell lines were examined.

Analogs can kill the cancer cells at concentrations 30 – 60 times lower than 5-FU, cisplatin, irinotecan.
Analogs bearing strong anti-tumor activities

They have a 84 times stronger activity than Curcumin.

Chapter 4: Molecular targets of analogs

Analogs have different mechanisms from approved cytotoxics.
This structure is important.

＞＞
GO‐035

GO‐Y041

IC50 : 1.6M

IC50 : ＞100M
No anti-tumor activities

Stronger anti-tumor activities

Michael reaction

No affinity to

High affinity toTargeted to Oncogene products(protein)DNAAnalogs target oncogene products.
Malignant phenotypes
1. Loss of growth control
2. Resistance to apoptosis
3. Immortality
4. Angiogenesis
5. Invasion
6. Metasatasis

Chapter 5: Oncogenes & analog
Her2 inhibitor

Myc inhibitor

Analogs can regulate overexpressed oncogene products
such as ,,,.
c-Myc, KRAS, CyclinD1, ErbB2, β-catenin, COX-2,, (examined).

KRAS inhibitor

NF-kB inhibitor

Analogs can induce apoptosis.
Malignant phenotypes

Chapter 6: Apoptosis & analogs
Caspases induction

1. Loss of growth control
2. Resistance to apoptosis
3. Immortality4. Angiogenesis
5. Invasion
6. Metasatasis
P53 induction
Analogs can induce apoptosis related proteinssuch as ,,,,,,,.
Caspases, PARP, TP53, XIAP, DR5,, (examined).

controlcurcumin

GO-Y030
Death receptor induction

Apoptotic DLD-1 cells

Chapter 7: Cancer stem cells & analogs
Analogs can kill cancer stem cells.
Cancer stem cell is likea queen bee. She is resistant
to chemotherapy.

sensitive

resistant

Killer Queen

Phosphorylation of STAT3 is characteristic to cancer stem cells.
Analogs can bind phosphorylation site of STAT3, and inhibit STAT3 signaling.

Analog

STAT3Analogs can inhibit
cancer stem cell growth in vivo.

Chapter 8: Potential against rare cancers

CTCL can be cured
in animal model.

Rare cancers‐ Multiple myeloma ‐MTT Assay
50.0

RPMI8226
KMS12
U266
OPM2GI50(μM)

40.0

30.0

20.0

10.0

0.0
Curcumin

Y030

Y078

Melphalan Thalidomide

72hr treatment

Chapter 9: Anti-angiogenic potential of analogs

Chapter 10:
Radioprotection

Chapter 11:
1. Improvement of solubility
Curcumin is low bioavailable (insoluble in water, poor absorption).

2. Antibody-Drug Conjugate

Antigenrecognitionsite

Papain digestion

Michael addition

reductionaddition

Chapter 12: Future Directions
1. An analog was detected in curry.
It is potent to suppress gastric cancer in vivo.
control
**
*
*
**
* **
*
analog**

Functional Food**

2. Analogs could induce anti-tumor immunity, like curcumin.
curcuminIncrease CD4+& CD8+

Increase Th1
cytokines

Decrease Treg

Decrease
T cell apoptosis

Apendix (1): Patent Right
We got US and Japan patents.

AnalogAnalog man

Appendix (2): Analog & Sleeping sickness (African trypanosomiasis)
Analogs may be effective for trypanosomiasis (sleeping sickness).

Growthinhibition
Analogs

Anti-trypanosomia
activity

carried by mosquitoes

Cytotoxicity

SafetyIndex

Recruit Collaborators!!