| Identification | Back Directory | [Name]
ARV-771 | [CAS]
1949837-12-0 | [Synonyms]
ARV-771
ARV 771; ARV771
(2S,4R)-1-[(2S)-2-[[2-[3-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide | [Molecular Formula]
C49H60ClN9O7S2 | [MDL Number]
MFCD30738017 | [MOL File]
1949837-12-0.mol | [Molecular Weight]
986.65 |
| Chemical Properties | Back Directory | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Store in freezer, under -20°C | [solubility ]
DMSO:65.92(Max Conc. mg/mL);68.22(Max Conc. mM)
DMF:20.0(Max Conc. mg/mL);20.7(Max Conc. mM)
DMF:PBS (pH 7.2) (1:6):0.14(Max Conc. mg/mL);0.14(Max Conc. mM)
Ethanol:55.0(Max Conc. mg/mL);56.92(Max Conc. mM) | [form ]
A crystalline solid | [pka]
13.61±0.46(Predicted) | [color ]
White to light yellow | [InChIKey]
PQOGZKGXGLHDGS-BZTQNJCZNA-N |
| Hazard Information | Back Directory | [Description]
ARV-771 is a BET PROTAC based on E3 ligase von Hippel-Lindau with Kds of 34 nM, 4.7 nM, 8.3 nM, 7.6 nM, 9.6 nM, and 7.6 nM for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1) and BRD4(2), respectively. | [Uses]
ARV-771 is an effective BET degrader of the PROTAC class. | [Biological Functions]
ARV-771, a von Hippel–Landau (VHL) E3 ligase-based BET PROTAC, is highly active against cellular models of CRPC. ARV-771 in these cells results in rapid BET protein degradation with DC50 (the drug concentration that results in 50% protein degradation) values <1 nM. Interestingly, ARV–771–mediated BET degradation leads to decreased both FL-AR and AR-V7 at the transcript level. In contrast, treating CRPC cells with BET inhibitors leads to the suppression of AR-V7 but not of FL-AR levels. Moreover, ARV-771 causes significantly greater apoptotic cell death than a BET inhibitor. ARV-771 dramatically suppresses the proliferation of castration-resistant prostate cancer models via inducing Von Hippel Lindau (VHL) E3 ligase-mediated degradation of BRDs and inhibiting AR signaling. A subsequent study has demonstrated that ARV-771 can also suppress the proliferation of mantle cell lymphoma cells via increasing the levels of tumour suppressors, including CDKN1A/p21, HEXIM1, and NOXA[1].
| [Biological Activity]
ARV-771 is a potent pan-(bromodomain and extra-terminal) BET degrader, a novel BET-PROTAC (proteolysis-targeting chimera), for BRD2(1), BRD2(2), BRD3(1) The Kd values of , BRD3(2), BRD4(1) and BRD4(2) were 34 nM, 4.7 nM, 8.3 nM, 7.6 nM, 9.6 nM and 7.6 nM, respectively. | [target]
| Target | Value | BRD2-BD2
(Cell-free assay) | 4.7 nM(Kd) | BRD3-BD2
(Cell-free assay) | 7.6 nM(Kd) | td> BRD4-BD2
(Cell-free assay) | 7.6 nM(Kd) | BRD3-BD1
(Cell-free assay) | 8.3 nM(Kd) | BRD4-BD1
(Cell-free assay) | 9.6 nM(Kd) |
| [storage]
Store at -20°C | [References]
[1] Yuanfei Deng. “ARV-771 Acts as an Inducer of Cell Cycle Arrest and Apoptosis to Suppress Hepatocellular Carcinoma Progression.” Frontiers in Pharmacology (2022).
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