ICG001 is a small molecule inhibitor that targets Wnt/β-catenin pathway. It inhibits TCF/β-catenin mediated transcription by competing with β-catenin for CBP (CREB binding protein) but not p300 binding with an IC50 of 3 μM [1]. It can be used to specifically evaluate the role of CBP/beta-catenin association on WNT signaling and cell physiology.
ICG001 have been shown to selectively inhibit colon carcinoma cell lines (SW480 and HCT-116 cells) but not normal colonic epithelial cells (CCD-841Co). It is also efficacious in the Min mouse and nude mouse xenograft models of colon cancer [1]. ICG-001 is a potent inhibitor of GBM stem cells in culture. ICG001 selectively inhibits Wnt/beta-catenin/CREB binding protein (CBP) signaling to reverses pulmonary fibrosis and ameliorate experimental dermal fibrosis in experimental models [2,3]. ICG001 is currently in clinical trial for colon cancer and leukemias.
References:
[1]Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7.
[2]Henderson WR Jr1, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA, Kahn M. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14.
[3]Beyer C, Reichert H, Akan H, Mallano T, Schramm A, Dees C, Palumbo-Zerr K, Lin NY, Distler A, Gelse K, Varga J, Distler O, Schett G, Distler JH. Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis. Ann Rheum Dis. 2013 Jul;72(7):1255-8.
ICG001 是一种靶向 Wnt/β-catenin 通路的小分子抑制剂。它通过与 β-连环蛋白竞争 CBP（CREB 结合蛋白）而不是 p300 结合来抑制 TCF/β-连环蛋白介导的转录,IC50 为 3 μM [1]。它可用于专门评估 CBP/β-连环蛋白结合对 WNT 信号和细胞生理学的作用。
ICG001 已显示可选择性抑制结肠癌细胞系（SW480 和 HCT-116 细胞）,但不抑制正常结肠上皮细胞 (CCD-841Co)。它在 Min 小鼠和裸鼠结肠癌异种移植模型中也有效 [1]。 ICG-001 是培养中 GBM 干细胞的有效抑制剂。 ICG001 选择性地抑制 Wnt/β-连环蛋白/CREB 结合蛋白 (CBP) 信号,以逆转肺纤维化并改善实验模型中的实验性真皮纤维化 [2,3]。 ICG001目前正在进行结肠癌和白血病的临床试验。