PRT4165

An inhibitor of PRC1 ubiquitin ligases

BMI1/RING1A and BMI1/RNF2 are E3 ubiquitin ligase complexes that mediate the monoubiquitination of histone 2A (H2A). This is an essential function of polycomb repressive complex 1 (PRC1).1 PRT4165 is an inhibitor of the ubiquitin ligase activity of PRC1.2,3 It blocks BMI1/RING1A self-ubiquitination (IC50 = 3.9 µM), as well as polyubiquitination of topoisomerase 2α in cells.2 PRT4165 inhibits ubiquitination of H2A by either RNF2 or RING1. Through these actions, PRT4165 prevents the accumulation of detectable ubiquitin at DNA double-strand breaks, the retention of response proteins around breaks, and the repair of breaks.3

235.2

≥98%

NSC 600157

O=C(C1=CC=CC=C1C/2=O)C2=C\C3=CC=CN=C3

C15H9NO2

31083-55-3

≥ 4 years

DMF: 10 mg/ml DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml DMSO: 2 mg/ml Ethanol: 1 mg/ml

1.Cao, J., and Yan, Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Frontiers in Oncology 2(26), 1-9 (2012).
2.Alchanati, I.,Teicher, C.,Cohen, G., et al. The E₃ ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2α cleavage complex - a potentially new drug target. PLoS One 4(12), (2009).
3.Ismail, I.H.,McDonald, D.,Strickfaden, H., et al. A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. The Journal of Biological Chemisty 288(37), 26944-26954 (2013).