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ARD-2585   Click here for help

GtoPdb Ligand ID: 11755

Synonyms: ARD2585 | compound 43 [PMID: 34473519]
PDB Ligand
Compound class: Synthetic organic
Comment: ARD-2585 is a highly potent and orally bioavailable PROTAC androgen receptor (AR) degrader molecule [1]. It was designed to reduce AR in metastatic castration-resistant prostate cancer (mCRPC), as an alternative mechanism to antagonising AR signaling with drugs such as enzalutamide and apalutamide. Structurally ARD-2585 is a bifunctional molecule that contains an AR antagonist ligand linked to a cereblon binding component, that targets the AR to the cereblon/cullin 4A E3 ligase complex for degradation. It shares structural similarities to bavdegalutamide, which was the first AR PROTAC to advance to clinical evaluation in humans.

ARD-2585 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 13
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 149.4
Molecular weight 762.3
XLogP 5.26
No. Lipinski's rules broken 2

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 N#Cc1ccc(cc1Cl)N([C@@H]1CC[C@H](CC1)NC(=O)c1ccc(cc1)N1CCN(CC1)C1CN(C1)c1ccc2c(c1)C(=O)N(C2=O)C1CCC(=O)NC1=O)C
Isomeric SMILES Clc1c(C#N)ccc(N(C)[C@H]2CC[C@@H](CC2)NC(=O)c2ccc(N3CCN(C4CN(C4)c4cc5c(C(=O)N(C6C(=O)NC(=O)CC6)C5=O)cc4)CC3)cc2)c1
InChI InChI=1S/C41H43ClN8O5/c1-46(30-9-4-26(22-43)35(42)21-30)28-10-5-27(6-11-28)44-38(52)25-2-7-29(8-3-25)47-16-18-48(19-17-47)32-23-49(24-32)31-12-13-33-34(20-31)41(55)50(40(33)54)36-14-15-37(51)45-39(36)53/h2-4,7-9,12-13,20-21,27-28,32,36H,5-6,10-11,14-19,23-24H2,1H3,(H,44,52)(H,45,51,53)/t27-,28-,36?
InChI Key LUCHABJUYSYJAT-RVWRWSNSSA-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/)
References
1. Xiang W, Zhao L, Han X, Qin C, Miao B, McEachern D, Wang Y, Metwally H, Kirchhoff PD, Wang L et al.. (2021)
Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer.
J Med Chem, 64 (18): 13487-13509. [PMID:34473519]