ICG-001

Biological Activity

ICG-001 selectively inhibits β-catenin/CBP interaction. ICG-001 exhibits growth inhibitory effects in colon carcinoma cell lines (SW480 and HCT-116 cells). ICG-001 also displays efficacy in Min mouse and nude mouse SW620 xenograft models. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells, and is efficacious in the Min mouse and nude mouse xenograft models of colon cancer. ICG-001 (5 mg/kg per day) significantly inhibits beta-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium. Administration of ICG-001 concurrent with bleomycin prevents fibrosis, and late administration is able to reverse established fibrosis and significantly improve survival.

Product Citations

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  Evid Based Complement Alternat Med. 2022 Jun 28;2022:9705948.

  ShenKang Injection Attenuates Renal Fibrosis by Inhibiting EMT and Regulating the Wnt/β-Catenin Pathway
  ICG-001 purchased from AbMole

• 

  bioRxiv. 2021 Jun 19;449094.

  Immune-evasion of KRAS-mutant lung adenocarcinoma mediated by cAMP response element-binding protein
  ICG-001 purchased from AbMole

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  J Biomed Sci. 2020 Jan 13;27(1):5.

  Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells.
  ICG-001 purchased from AbMole

• 

  Onco Targets Ther. 2019 Aug 30;12:7067-7077.

  Upregulation of SHIP2 participates in the development of breast cancer via promoting Wnt/β-catenin signaling.
  ICG-001 purchased from AbMole

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  Oncogene. 2015 Sep 17.

  Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer.
  ICG-001 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Oncogene (2014). Figure 1. ICG-001 was purchased from AbMole BioSciences (Kowloon, Hong Kong, China)
	Method	microscopy images
	Cell Lines	IEC-6 caMEK
	Concentrations	7.5 µ M
	Incubation Time	36 h
	Results	"The caMEK-transformed cells showed a partial reversion to an epithelial morphology after treatment of caMEK-transformed cells with ICG-001, a small-molecule antagonist of β-catenin/ TCF-mediated transcription."

Protocol (for reference only)

Cell Experiment
Cell lines	NCI-H929, U266, MM1S, and RPMI-8226
Preparation method	Cells were treated with various concentrations of ICG-001 for 24 hours. 3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) dye (Sigma) was added for the last 4 hours of incubation. Insoluble formazan complexes were pelleted and solubilized with DMSO, and absorbance was measured at 540 nm using a Benchmark Plus microplate spectrophotometer (Bio-Rad, Hercules, CA). The IC50 values were calculated using CalcuSyn software (Biosoft, Cambridge, UK). Each experimental condition was done in triplicate and repeated at least once.
Concentrations	0-50 µ M
Incubation time	24 h

Animal Experiment
Animal models	MM tumors were established in SCID-beige mice by subcutaneous inoculation of 1x107 MM RPMI-8226 cells in the right flank
Formulation	Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich).
Dosages	100 mg/kg ICG-001 twice a day
Administration	administered intraperitoneally

Chemical Information

Molecular Weight	548.63
Formula	C33H32N4O4
CAS Number	780757-88-2
Solubility (25°C)	DMSO ≥ 50 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Zhou B, et al. J Biol Chem. Interactions between β-catenin and transforming growth factor-β signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP).

[2] Henderson WR Jr, et al. Proc Natl Acad Sci U S A. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis.

[3] Emami KH, et al. Proc Natl Acad Sci U S A. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription.