Description
Product Usage Information
PRT-4165 is supplied as a lyophilized powder. For a 10 mM stock, reconstitute 1 mg of powder in 0.43 mL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect.
Storage
Store lyophilized at room temperature, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles .
Background
The small-molecule PRT-4165 inhibits the E3 ligase activity of Bmi1/Ring1A (IC = 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).
Alternate Names
2-(3-Pyridinylmethylene)-1H-Indene-1,3(2H)-dione
