prt4165

Description: PRT4165 (NSC600157) is a potent and selective inhibitor of the PRC1 (polycomb repressive complex 1)-mediated H2A ubiquitylation with potential anticancer activity. It has an IC50 of 3.9 uM for inhibiting PRC1 in a cell-free assay. It inhibits PRC1-mediated H2A ubiquitylation in vivo and in vitro. PRT-4165 also inhibits the accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the retention of several DNA damage response proteins in foci that form around DSBs, and the repair of the DSBs. PRC1-mediated histone ubiquitylation plays an important role in aberrant gene silencing in human cancers and is a potential target for cancer therapy. PRT4165 as a novel chromatin-remodeling compound provides a new tool for the inhibition of ubiquitylation signaling at DNA double-strand breaks.

References: J Biol Chem. 2013 Sep 13; 288(37):26944-54.