Description
PRT-4165 (31083-55-3) is an inhibitor of Bmi1/Ring1A, subunits of the polycomb repressive complex 1 (PRC1). Inhibits self-ubiquitination (IC50?= 3.9 μM) but does not increase cellular levels of either subunit. Blocks Bmi1/Ring1A-mediated ubiquitination and drug-induced degradation of topoisomerase 2α.1?PRT-4165 inhibits H2A/H2AX ubiquitination via blocking the E3 ubiquitin ligase activity of RNF2 and a Bmi1/RNF2 complex. Blocks polycomb repressor complex (PRC) 1-mediated histone H2A ubiquitination?in vitro?and?in vivo?and as such represents a new tool for studying chromatin remodeling.2
Biochem/physiol Actions
PRT4165 is a potent inhibitor of PRC1 (polycomb-repressive complex 1)-mediated histone H2A ubiquitylation in vivo and in vitro. PRT4165 inhibits the in vitro histone H2A E3 ubiquitin ligase activity of PRC1 components RING1, RNF2, and a BMI1/RNF2 complex. PRT4165 also inhibits DNA double-strand breaks induced ubiquitylation of histone H2AX.
References
1) Alchanati?et al. (2009),?The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex – a potentially new drug target; PLoS One,?4?e8104
2) Ismail?et al.?(2013),?A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks; J. Biol. Chem.,?288?26944
