Signaling through small G proteins of the RhoA subfamily, including RhoC, induces actin-regulated cytosolic-to-nuclear translocation of the oncogene product megakaryoblastic leukemia 1 (MKL1), which binds to serum response factor (SRF). The MKL1/SRF complex, in turn, activates the transcription of serum response element (SRE) regulated genes, stimulating cell migration, a process that is central to metastasis. CCG-203971 is an inhibitor of SRE activation in the prostate cancer cell line PC-3 (IC50 = 6.4 μM), with 87% inhibition of SRE activation achieved at 100 μM. This compound also inhibits PC-3 cell migration (IC50 = 4.2 μM), as determined by a scratch wound assay. CCG-203971 causes no cytotoxicity when evaluated by WST-1 assay. It is well tolerated in normal mice up to doses of 100 mg/kg given intraperitoneally over five days.
