CCG-1423 is a small-molecule inhibitor of RhoA transcriptional signaling. The interaction between MRTF-A and importin a/b1 was inhibited by CCG-1423, but monomeric G-actin binding to MRTF-A was not inhibited [4].
Multiple members of the Rho family of small GTPases play important roles in these cellular processes and in some human tumors (e.g., colon, esophageal, lung, pancreatic, and inflammatory breast cancers), up-regulation of RhoA or RhoC is associated with a poor clinical outcome (2, 3).
CCG-1423 has nanomolar to low micromolar potency as well as selectivity toward Rho-overexpressing and invasive cancer cell lines for inhibition of DNA synthesis, cell growth, and/or invasion. Caspase-3 activation in the highly metastatic RhoC-overexpressing A375M2 melanoma cell line was enhanced by CCG-1423 whereas a smaller increase was seen with the parental A375 cell line, whereas just the opposite pattern was seen with daunorubicin [2].
References:
[1]. Minami T, Kuwahara K, Nakagawa Y et al. Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice. EMBO J. 2012 Nov 28;31(23):4428-40. doi: 10.1038/emboj.2012.296. Epub 2012 Oct 26.
[2]. Hayashi K, Watanabe B, Nakagawa Y et al. RPEL proteins are the molecular targets for CCG-1423, an inhibitor of Rho signaling. PLoS One. 2014 Feb 18;9(2):e89016. doi: 10.1371/journal.pone.0089016. eCollection 2014.