(S)-CCG-1423

(S)-CCG-1423 is a stereoisomer of CCG-1423. CCG-1423 is a Rho inhibitor involved in blocking signaling through myocardin-related transcription factor A (MRTF-A) and serum response factor (SRF) [1].

The Rho family of small GTPases plays an important role in cancer metastasis. Up-regulation of RhoA or RhoC has been associated with a poor clinical outcome. Rho GTPases are important for the actin cytoskeleton. The RhoA family plays an important role in multiple cellular processes central to tumor growth and metastasis [1].

CCG-14223 was an inhibitor for Rho/SRF pathway and displayed activity in several in vitro cancer cell functional assays. In PC-3 prostate cancer cells, CCG-1423(< 1 μmol/L) potently inhibited lysophosphatidic acid–induced DNA synthesis. CCG-1423 inhibited the growth of RhoC-overexpressing melanoma lines (A375M2 and SK-Mel-147) at nanomolar concentrations. CCG-1423 selectively stimulated apoptosis of the metastasis-prone, RhoC-overexpressing melanoma cell line (A375M2) when compared with the parental cell line (A375). CCG-1423 inhibited Rho-dependent invasion by PC-3 prostate cancer cells [1].

The S-isomer of CCG-1423 inhibited MRTF-A-dependent cellular events, including SRF-mediated gene expression and cell migration. The efficacy of (S)-CCG-1423 was more potent than the R-isomer [2].

References:
[1] Evelyn C R, Wade S M, Wang Q, et al.  CCG-1423: a small-molecule inhibitor of RhoA transcriptional signaling[J]. Molecular cancer therapeutics, 2007, 6(8): 2249-2260.
[2] Watanabe B, Minami S, Ishida H, et al.  Stereospecific inhibitory effects of ccg-1423 on the cellular events mediated by myocardin-related transcription factor a[J]. PloS one, 2015, 10(8): e0136242.