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Bioorg Med Chem Lett. 2010 Jan 15;20(2):665-72. doi: 10.1016/j.bmcl.2009.11.056. Epub 2009 Nov 18.

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

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1
Department of Pharmacology, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA.

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.

PMID:
19963382
PMCID:
PMC2818594
DOI:
10.1016/j.bmcl.2009.11.056
[Indexed for MEDLINE]
Free PMC Article

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