CCG-222740 is a potent and selective Rho/myocardin-related transcription factor (MRTF) pathway inhibitor[1]. CCG-222740 also is a potent inhibitor of alpha-smooth muscle actin protein expression. CCG-222740 effectively reduces fibrosis in skin and blocks melanoma metastasis[2].
CCG-222740 (10, 20 μM; for 72 hours) increases the protein levels of p27 and decreased cyclin D1. CCG-222740 decreases cell viability of CAFs, with an IC50 of ~10 μM[1]. CCG-222740 (10, 25 μM) is potent at decreasing αSMA protein expression in human conjunctival fibroblasts[2]. CCG-222740 has an IC50 of 5 μM in a fibroblast-mediated collagen contraction assay, and it is less cytotoxic[2]. Cell Cycle Analysis[1] Cell Line: Cancer associated fibroblasts (CAFs)
CCG-222740 (Oral gavage; 100 mg/kg daily for 7 days) significantly reduces α-SMA levels in the pancreas of caerulein-stimulated KC mice[1]. Animal Model: KC mice (LSL-KrasG12D/+; Pdx-1-Cre) of age at 9 weeks[1]
[1]. Leal AS, et al. The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice. Sci Rep. 2019 May 8;9(1):7072. [2]. Yu-Wai-Man C, et al. Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Sci Rep. 2017 Mar 31;7(1):518.