2. Academic Validation
  3. Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423

Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):665-72. doi: 10.1016/j.bmcl.2009.11.056.
Chris R Evelyn 1,  Jessica L Bell,  Jenny G Ryu,  Susan M Wade,  Andrew Kocab,  Nicole L Harzdorf,  H D Showalter,  Richard R Neubig,  Scott D Larsen
Affiliations

Affiliation

  • 1 Department of Pharmacology, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
PMID: 19963382 DOI: 10.1016/j.bmcl.2009.11.056
Abstract

We recently identified bis(amide) CCG-1423 (1) as a novel inhibitor of RhoA/C-mediated gene transcription that is capable of inhibiting invasion of PC-3 prostate Cancer cells in a Matrigel model of metastasis. An initial structure-activity relationship study focusing on bioisosteric replacement of the amides and conformational restriction identified two compounds, 4g and 8, with improved selectivity for inhibition of RhoA/C-mediated gene transcription and attenuated cytotoxicity relative to 1. Both compounds were also capable of inhibiting cell invasion with equal efficacy to 1 but with less attendant cytotoxicity.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13991
    99.94%, Rho/MRTF/SRF Pathway Inhibitor