BWA-522   Click here for help

GtoPdb Ligand ID: 12912

Synonyms: BWA522 | compound 28 [PMID: 37556600]
Compound class: Synthetic organic
Comment: BWA-522 is an orally active cereblon-targeting PROTAC degrader of the androgen receptor (AR) [2]. It was designed for potential to treat advanced prostate cancer. BWA-522 binds to the N-terminal domain (NTD) of the AR using a warhead derived from the antagonist EPI-002 (ralaniten) [1]. Exploiting the NTD is proposed as a strategy to target both wild type ARs and mutated ARs that have no ligand-binding domain (LBD) and that are therefore unsusceptible to androgen-competitive antagonist drugs.
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 CDK toolkit. 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 11
Hydrogen bond donors 2
Rotatable bonds 13
Topological polar surface area 128.72
Molecular weight 771.34
XLogP 4.49
No. Lipinski's rules broken 3
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.

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Canonical SMILES CC(C)(C1=CC=C(C=C1)OCC2CCN(CC2)CC3CCN(CC3)C4=CC=C5C(=C4)C(=O)N(C6CCC(=O)NC6=O)C5=O)C7=CC=C(C=C7)OC[C@@H](CCl)O
Isomeric SMILES ClC[C@H](COC1=CC=C(C=C1)C(C)(C)C2=CC=C(OCC3CCN(CC3)CC4CCN(CC4)C=5C=C6C(N(C(C6=CC5)=O)C7C(NC(CC7)=O)=O)=O)C=C2)O
InChI InChI=1S/C43H51ClN4O7/c1-43(2,31-5-10-35(11-6-31)55-27-33(49)24-44)30-3-8-34(9-4-30)54-26-29-15-19-46(20-16-29)25-28-17-21-47(22-18-28)32-7-12-36-37(23-32)42(53)48(41(36)52)38-13-14-39(50)45-40(38)51/h3-12,23,28-29,33,38,49H,13-22,24-27H2,1-2H3,(H,45,50,51)/t33-,38?/m1/s1
InChI Key MYCPBYLZNZTLBC-OVFDOZPJSA-N
References
1. Myung JK, Banuelos CA, Fernandez JG, Mawji NR, Wang J, Tien AH, Yang YC, Tavakoli I, Haile S, Watt K et al.. (2013)
An androgen receptor N-terminal domain antagonist for treating prostate cancer.
J Clin Invest, 123 (7): 2948-60. [PMID:23722902]
2. Zhang B, Liu C, Yang Z, Zhang S, Hu X, Li B, Mao M, Wang X, Li Z, Ma S et al.. (2023)
Discovery of BWA-522, a First-in-Class and Orally Bioavailable PROTAC Degrader of the Androgen Receptor Targeting N-Terminal Domain for the Treatment of Prostate Cancer.
J Med Chem, 66 (16): 11158-11186. [PMID:37556600]