ARV-771

ARV-771 is a proteolysis-targeting chimera (PROTAC) that drives the degradation of bromodomain and extra terminal domain (BET) family proteins. It is comprised of a BET-binding moiety conjugated via a linker to a von Hippel-Lindau (VHL) E3 ligase-binding moiety. ARV-771 induces degradation of bromodomain-containing protein 2 (BRD2), BRD3, and BRD4 in 22Rv1 castration-resistant prostate cancer (CRPC) cells with half-maximal degradation (DC50) values of less than 5 nM for all. It inhibits proliferation of and increases poly(ADP-ribose) polymerase (PARP) cleavage in 22Rv1 cells in a concentration-dependent manner. ARV-771 reduces full-length androgen receptor protein levels and prevents increases in ERG induced by the synthetic androgen R1881 in VCaP cells in a concentration-dependent manner. ARV-771 (30 mg/kg per day, s.c.) induces tumor regression in a 22Rv1 mouse xenograft model.Formal Name: (2S,4R)-1-((S)-2-(tert-butyl)-15-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide. CAS Number: 1949837-12-0. Molecular Formula: C49H60ClN9O7S2. Formula Weight: 986.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMF:PBS (pH 7.2) (1:6): 0.14 mg/ml, DMSO: 15 mg/ml, Ethanol: 10 mg/ml. lambdamax: 257 nm. SMILES: CC1=NN=C2[C@H](CC(NCCOCCCOCC(N[C@@H](C(C)(C)C)C(N3C[C@H](O)C[C@H]3C(N[C@@H](C)C4=CC=C(C5=C(C)N=CS5)C=C4)=O)=O)=O)=O)N=C(C6=CC=C(Cl)C=C6)C7=C(SC(C)=C7C)N21. InChi Code: InChI=1S/C49H60ClN9O7S2/c1-27-30(4)68-48-41(27)42(33-14-16-35(50)17-15-33)54-37(45-57-56-31(5)59(45)48)23-39(61)51-18-21-65-19-9-20-66-25-40(62)55-44(49(6,7)8)47(64)58-24-36(60)22-38(58)46(63)53-28(2)32-10-12-34(13-11-32)43-29(3)52-26-67-43/h10-17,26. InChi Key: PQOGZKGXGLHDGS-QQRWPDCKSA-N.