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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Physico-chemical Properties
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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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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]