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

PRI-724 特异性地与 CBP 结合，而不与相关的转录共激活因子 p300 结合，从而破坏了 CBP 与 β-catenin 的相互作用。使用 PRI-724 处理可以选择性地诱导结肠癌细胞的凋亡，但不会对正常的结肠上皮细胞产生影响，并且减少了结肠癌细胞在体外的生长[1][2]。

PRI-724在结肠癌小鼠异种移植模型中显示出抗肿瘤活性。PRI-724的一期临床试验初步结果已公开披露。该化合物显示出可接受的毒性特性，仅有一种限制剂量的毒性为Ⅲ级可逆性高胆红素血症。一项针对晚期髓系恶性肿瘤患者的PRI-724开放标签剂量递增I/II期研究仍在进行中[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.