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

CR Evelyn, JL Bell, JG Ryu, SM Wade, A Kocab…

Index: Evelyn, Chris R.; Bell, Jessica L.; Ryu, Jenny G.; Wade, Susan M.; Kocab, Andrew; Harzdorf, Nicole L.; Hollis Showalter; Neubig, Richard R.; Larsen, Scott D. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 2 p. 665 - 672

Full Text: HTML

Citation Number: 38

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 ...