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.
|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 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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 100 mg/mL
Ethanol 40 mg/mL
|Source||Oncogene (2014). Figure 1. ICG-001 was purchased from AbMole BioSciences (Kowloon, Hong Kong, China)|
|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."|
Oncogene. 2015 Sep 17.
Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer.
ICG-001 purchased from AbMole
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).
Zhou B, et al. J Biol Chem. 2012 Mar 2;287(10):7026-38. PMID: 22241478.
Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis.
Henderson WR Jr, et al. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14. PMID: 20660310.
A small molecule inhibitor of beta-catenin/CREB-binding protein transcription.
Emami KH, et al. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7. PMID: 15314234.
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