Background
The small-molecule PRT-4165 inhibits the E3 ligase activity of Bmi1/Ring1A (IC50 = 3.9 μM), inhibits ubiquitination of topoisomerase Top2α, and alters Bmi1 localization from nucleolar bodies to more disperse nuclear and cytoplasmic localizations (1). PRT-4165 inhibits both Ring1A and RNF2 (Ring1B), which account for the polycomb-repressive complex 1 (PRC1) E3 ubiquitin ligase activity. PRC1-mediated ubiquitylation of histones plays an important role in DNA repair and gene silencing, and may be relevant in determining cell fate and development of human cancers. Treatment of cells with PRT-4165 inhibited H2A ubiquitylation in cells and at sites of DNA damage, resulting in delayed double-strand break (DSB) repair and impaired response to genotoxic stress (2). PRT-4165 treatment of leukemia cells suppressed cell growth and downregulated NOTCH signaling protein expression (3). PRT-4165 treatment of differentiating human embryonic stem cells promoted neuroectodermal differentiation, indicating that Ring1B regulation could be used to direct stem cells toward an early neuronal fate (4).
Molecular Formula
C15H9NO2
Molecular Weight
235.2 g/mol
Purity
>98%
CAS
31083-55-3
Solubility
Soluble in DMSO at 25 mg/mL or ethanol at 6 mg/mL.
Storage
Directions for Use
Background References
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
Trademarks and Patents
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