CCG-203971

1443437-74-8

C23H21ClN2O3

DMSO : >= 155 mg/mL (379.08 mM); H2O : < 0.1 mg/mL (insoluble)

GPCR/G Protein

CCG-203971 is a second-generation RhoA/myocardin-related transcription factor A (MRTF-A) inhibitor. CCG-203971 potently targets RhoA/C-activated serum response element (SRE)-luciferase (IC₅₀=6.2 uM). IC50 & Target: RhoA/MRTF-A^[1] In Vitro: CCG-203971, a second-generation Ras homolog gene family, member A (RhoA)/myocardin-related transcription factor A (MRTF-A)/serum response factor (SRF) pathway inhibitor, represses both matrix-stiffness and transforming growth factor beta–mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner. CCG-203971 significantly represses TGF-beta- induced MKL1 expression at 25 uM concentration^[1]. Human dermal fibroblasts are plated onto 96-well plates and allowed to grow for 3 days in the presence of 30 uM CCG-203971 or DMSO vehicle. Viable cell density is assessed through enzymatic reduction of the water-soluble tetrazolium dye WST-1. Scleroderma dermal fibroblasts proliferate faster than normal cells, and this is inhibited by CCG-203971^[2]. In Vivo: CCG-203971 is tested in a Bleomycin skin injury model. Bleomycin is administered in 50 uL of DMSO intraperitoneally. Preliminary studies show that Bleomycin administered in this manner is well tolerated at 100 mg/kg twice a day. Intradermal Bleomycin for 2 weeks along with the DMSO control (50 uL i.p.) results in marked dermal thickening (P<0.0001) compared with the PBS+DMSO group, which does not receive Bleomycin. CCG-203971 treatment strongly and significantly (P<0.001) suppresses the Bleomycin-induced skin thickening in this model. Skin collagen amounts, assessed by measurement of hydroxyproline content, show similar results. Bleomycin injections promote collagen deposition (P<0.01) and CCG-203971 is able to block this effect (P<0.05)^[2].