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Biological Activity:

PRT4165 is a potent and selective E3 Ubiquitin-ligase Bmi1/Ring1A Inhibitor, inhibits self-ubiquitination (IC50 ~3.9 μM) but does not increase cellular levels of either subunit. Bmi1/Ring1A are subunits of the polycomb repressive complex 1 (PRC1) and play an important role in aberrant gene silencing in human cancers. PRT4165 could prevent Bmi1/Ring1A-mediated ubiquitination and drug-induced degradation of topoisomerase 2α (Top2α). It also inhibits the in vitro E3 ubiquitin ligase activity of RNF2 and a Bmi1/RNF2 complex, inhibiting H2A/H2AX ubiquitination. It can block polycomb repressor complex (PRC) 1-mediated histone H2A ubiquitination in vitro. PRT4165 is a novel chromatin-remodeling compound and provides a new tool for the inhibition of ubiquitylation signaling at DNA double-strand breaks.

How to Use:

In vitro: PRT4165 was used at 10-50 μM final concentration in various in vitro assays.
In vivo: n/a

Reference:

• 1. Alchanati I, et al. The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target. (2009) PLoS One. 4(12):e8104.
• 2. Ismail IH, et al. A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. (2013) J Biol Chem. 288(37):26944-54.?