ICG001 antagonizes Wnt/β-catenin/TCF-mediated transcription and specifically binds to element-binding protein (CREB)-binding protein (CBP) with IC50 of 3 μM, but is not the related transcriptional coactivator p300.

CBP:3 μM

ICG001 binds specifically to CBP but not the related transcriptional coactivator p300, thereby disrupting the interaction of CBP with β-catenin. Treatment with ICG001 selectively induces apoptosis in colon carcinoma cells but not in normal colonic epithelial cells and reduces in vitro growth of colon carcinoma cells[1][2].

ICG001 exhibits antitumor activity in the mouse xenograft models of colon cancer. The initial results of the Phase I clinic trial of ICG001 has been disclosed publically. The drug exhibits an acceptable toxicity profile with only one dose-limiting toxicity of grade 3 reversible hyperbilirubinaemia. An Open-Label dose-escalation phase I/II study of ICG001 for patients with advanced myeloid malignancies is still ongoing[2].

ICG-001 is dissolved in DMSO. To evaluate effects of ICG-001 on α-SMA and collagen type 1 expression, RLE-6TN cells are treated with TGF-β1 (0.25 ng/mL) in the presence or absence of ICG-001 (5.0 μM). After 24 h, cells are harvested and mRNA isolated for analysis by qPCR. RNA is reverse-transcribed using SuperScript reverse transcriptase. Quantitative PCR is performed with SYBR-Green PCR using Real-Time PCR System HT7900. The amplification protocol is set as follows: 95°C denaturation for 10 min followed by 40 cycles of 15-s denaturation at 95°C, 1 min of annealing/extension, and data collection at 60°C.