ICG001 is a β-catenin/TCF-mediated transcription inhibitor that selectively blocks β-catenin/CBP interaction without interfering with β-catenin/p300 interaction. It specifically binds to CREB protein with an IC50 of 3 μM.

CBP:3 μM

METHODS: SW480 cells were treated with ICG-001 (25 μM, 24 h) and the inhibition of survivin gene transcription was measured by semiquantitative RT-PCR; SW480 and HCT116 cells were treated with ICG-001 (10 and 25 μM, 24 h) and analyzed by immunoblotting for survivin; SW480 cells were treated with ICG-001 (25 μM) and the chromatin immunoprecipitation assay of the cyclin D1 promoter was used; promoter occupancy was assessed with CBP- (AC-22) or p300- (C-20) specific antibodies in the presence of ICG-001 (25 μM, 8 h). RESULTS After 8 h of treatment of SW480 cells with 25 μM ICG-001, approximately 2% of the genes analyzed were upregulated by a factor greater than 2, while only approximately 0.3% of the genes were downregulated by more than 50%. The two genes downregulated were S100A4 and survivin, which are the first and fourth mRNAs upregulated in cancer cells, respectively. ICG-001 effectively reduced the steady-state levels of survivin mRNA and protein in treated colorectal cancer cells. SW480 cells treated with ICG-001 (25 μM) showed a significant decrease in cyclin D1 as early as 4 h after treatment. Using chromatin immunoprecipitation, ICG-001 was shown to selectively inhibit the endogenous cyclin D1 promoter β[1].

METHODS: In a tumor regression SW620 nude mouse xenograft model, ICG-001 (150 mg/kg, intravenous injection) was administered to observe the effect of the drug on tumor remission in nude mice.
RESULTS Tumor volume was significantly reduced during the 19-day treatment, with no mortality or weight loss. [1]