产品描述

PRT4165 is a Bmi1/Ring1A inhibitor with an IC50 of 3.9 µM in the cell-free assay and also inhibits PRC1-mediated H2A ubiquitylation in vivo and in vitro.

靶点（IC50 & Targe）

BMI-1,

Ring1A

体外研究

PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation in vivo and in vitro. It inhibits the accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the retention of several DNA damage response proteins in foci that form around DSBs, and the repair of the DSBs. PRT4165 inhibits both RNF2 and RING 1A, which are partially redundant paralogues that together account for the E3 ubiquitin ligase activity found in PRC1 complexes, but not RNF8 nor RNF168. U2OS cells treated with increasing concentrations of PRT4165 show increasing numbers of cells in G2/M[2].

细胞实验

Cell lines: HeLa cells

Concentrations: 50 μM

Incubation Time: 5 h

Method: HeLa cells are transfected with Bmi1-FLAG, Ring1A and HA-ubiquitin. Twenty-four hours post transfection the cells are treated with either solvent (0.5% DMSO, 0.5% PEG400) or 50 μM PRT4165 for 5 hours. Bmi1-FLAG is immunoprecipitated from cell lysates, and conjugated ubiquitin is detected by Western-blot with anti-HA antibody.

(Only for Reference)

动物实验

Animal Models: CD-1 mice

Formulation: sesame oil containing 10% ethanol

Dosages: 4 mg/kg and 8 mg/kg

Administration: intraluminally injection

(Only for Reference)

参考文献

[1] Alchanati I, et al. PLoS One. 2009, 4(12):e8104.

[2] Ismail IH, et al. J Biol Chem. 2013, 288(37):26944-54.

[3] Fenghua Bian, et al. Sci Rep. 2016, 6: 26061.