ARV-771   Click here for help

GtoPdb Ligand ID: 10564

Synonyms: ARV771
Compound class: Synthetic organic
Comment: ARV-771 is a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology [1]. It targets the BET domain proteins BRD2/3/4 for VHL E3 ligase-mediated ubiquitination and proteasomal degradation. This mechanism effects suppression of the androgen receptor (AR) protein level and AR signalling. ARV-771 is efficacious in vivo, as demonstrated in two different mouse models of castration-resistant prostate cancer (CRPC).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

ARV-771 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 15
Hydrogen bond donors 4
Rotatable bonds 23
Topological polar surface area 258.22
Molecular weight 985.37
XLogP 6.3
No. Lipinski's rules broken 3

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC1CC(N(C1)C(=O)C(C(C)(C)C)NC(=O)COCCCOCCNC(=O)CC1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C)C(=O)NC(c1ccc(cc1)c1scnc1C)C
Isomeric SMILES O[C@@H]1C[C@H](N(C1)C(=O)[C@H](C(C)(C)C)NC(=O)COCCCOCCNC(=O)C[C@@H]1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C)C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C
InChI 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/h10-17,26,28,36-38,44,60H,9,18-25H2,1-8H3,(H,51,61)(H,53,63)(H,55,62)/t28-,36+,37-,38-,44+/m0/s1
InChI Key PQOGZKGXGLHDGS-QQRWPDCKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
ARV-771 degrades BRD2/3/4 in cellular assays with a DC50 <5 nM and promotes significantly greater apoptotic cell death than a BET inhibitor alone [1]. It reduces BET function with an IC50 <1 nM which is more potent than the BET inhibitor (+)-JQ1, although its binding affinity (Kd) is similar to that reported for (+)-JQ1.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
bromodomain containing 2 Hs Inhibitor Inhibition 8.3 pKd - 1
⤷ pKd 8.3 (Kd 4.7x10-9 M) [1]
Description: Binding affinity for bromodomain 2 of hBRD2.
bromodomain containing 4 Hs Inhibitor Inhibition 8.1 pKd - 1
⤷ pKd 8.1 (Kd 7.6x10-9 M) [1]
Description: Binding affinity for bromodomain 2 of hBRD4.
bromodomain containing 3 Hs Inhibitor Inhibition 8.1 pKd - 1
⤷ pKd 8.1 (Kd 7.6x10-9 M) [1]
Description: Binding affinity for bromodomain 2 of hBRD3.