Antibody drug and nucleic acid drug candidates
targeting the DKK1-CKAP4 pathway
CKAP4

αCKAP4_mAB

DKK1

GREB1

DKK1-CKAP4pathway

GREB1pathway
CKAP4Wnts

Fz

GREB1p300
Smad2/3
核Smad4

p85 PI3K
p110

LRP5/6Axin
APC

GREB1 ASO

AKT

Wnt
β-catheninsignal pathway
proliferation

×（antisense）

YAP/TAZ

β-cathenin
核 Tcf/Lef

Rho

GTP

GREB1

Target gene

Arl4c
DKK1

Rac1
GTP
Arl4c
GTP

Arl4c ASO
（antisense）

Arl4cpathway

Cell
movement

Arl4c

Anti-cancer drug candidate : anti-CKAP4 antibody
CKAP4: Discovered as a novel receptor for the long-unknown tumor growth-promoting
secreted protein DKK1. Research on the DKK1-CKAP4 novel cancer signaling axis is stillongoing at Osaka University.
DKK1 activates AKT through binding of CKAP4 and PI3K to promote cell
Overexpression of DKK1 and CKAP4 is frequently observed in pancreatic, lung, esophageal,
and liver cancers, correlated with poor prognosis

In vivo efficacy confirmed,
Now, humanized antibody is available
Anti-CKAP4 antibodies inhibit tumorigenesisof pancreatic, lung, esophageal, and livercancers in mouse models
Humanized anti-CKAP4 antibody has alreadybeen produced, currently being analyzed forefficacy.

Not only licensing as an antibody drug, as
well as joint research for synergistic effects
evaluation
Samples can be provided for trial evaluation(for a fee).
Patent No.: US 10,618,954 B2

Novel Nucleic Acid Drug Candidates：Arl４c
Arl4c：

Low molecular weight G protein belonging to the Arf family
Expressed by the co-operative action of Wnt and EGF signaling

Arl4c activates the Rac and Rho low molecular weight signaling
pathways and promotes cancer cell proliferation and invasion.
Overexpression is frequently observed in lung, colon, liver, andpancreatic cancers and correlates with poor prognosis.

Arl4c ASO inhibits tumorigenesis of lung, colon, and liver cancers in mouse models.
Inhibits metastasis of pancreatic cancer.

Liver Cancer

Lung Cancer

Pancreatic cancer

Wnt + EGF Downstream Effects
Rac1/Rho
β-カテニン Ras

Arl4c

YAP/TAZ

Colorectal cancer
Lung cancer
Invasion, metastasis, proliferation
Liver cancer
Patent application: "Antisense oligonucleotides targeting ARL4C and nucleic acid medicine using
Pancreatic cancer
said antisense oligonucleotides. antisense oligonucleotide targeting ARL4C, and nucleic acid
Oral Cancer・・・・・
medicine using said antisense oligonucleotide. PCT/JP2019/034746

Novel Nucleic Acid Drug Candidates GREB1
GREB1 is a target gene (protein) of hormone receptors and is itself an activator of hormone receptors. GREB1
is highly expressed in breast and prostate cancers, which are hormone-dependent tumors, and promotes tumor
growth.GREB1 is expressed in hormone-independent tumors such as hepatoblastoma, hepatocellular carcinoma,malignant melanoma, and neuroblastoma.
In hepatoblastoma, hepatocellular carcinoma, malignant melanoma, and neuroblastoma, GREB1 was expressedby cancer cell-specific transcription factors; GREB1 expression correlated with the aggressiveness of thehormone-independent tumors described above.

hepatoma

infantile hepatoblastoma

Cancer Res.
2023

Nature Commun.
2019

hepatoblastoma
carcinogenesis model Control

RNA/ChIP Seq
GREB1 KDEnhancer
H3K27ac
HNF4α
FOXA2
TCF4
GREB1

Patent pending: PCT/JP2020/020274 (2020. 5. 22)

TSS GREB1 geneProposal: Licencing, Collaboration
Antibody drug ：CKAP4
Now, humanized antibody is available.
Would you like to investigate synergistic effects
with your anti-cancer drugs and antibodies?

Antisense drug : Arl4c、GREB1
Antisense to liver for easy delivery
Research using the latest nucleic acids from the Obika’s Lab isunderway.