ARV-771

ARV-771 is a potent bromodomain and extra-terminal (BET) proteins degrader based on PROTAC technology with Kd values of 4.7, 7.6, 7.6 nM against BRD2, BRD3 and BRD4, respectively.

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO : ≥ 50 mg/mL (50.68 mM)

ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. ARV-771 potently degrades BRD2/3/4 in 22Rv1 cells with a DC50 less than 5 nM. c-MYC protein is a downstream effector of BET proteins. Treatment with ARV-771 results in depletion of c-MYC with an IC50 of less than 1 nM. ARV-771 shows strong antiproliferative effect on 22Rv1, VCaP, and LnCaP95 cell lines. ARV-771 treatment has a pronounced effect on cell morphology consistent with apoptosis. FL-AR and AR-V7 mRNA are down-regulated upon treatment with 10 nM ARV-771 in VCaP cells. ARV-771 has an antiandrogenic effect on a number of AR-regulated genes in VCaP cells.

Treatment of non castrated male Nu/Nu mice bearing AR-V7+ 22Rv1 tumor xenografts with daily subcutaneous injections of ARV-771 at 10 mg/kg for 3 d results in 37% and 76% down-regulation of BRD4 and c-MYC levels, respectively, in tumor tissue. A marked down-regulation in levels of AR-V7 is observed in the 22Rv1 tumors after ARV-771 treatment.