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… - Bioorganic & medicinal …, 2010 - Elsevier
CR Evelyn, JL Bell, JG Ryu, SM Wade, A Kocab, NL Harzdorf, HDH Showalter, RR Neubig
Bioorganic & medicinal chemistry letters, 2010Elsevier
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 …
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.
Elsevier