ar antagonist1

AR antagonist 1 is a potent antagonist of the androgen receptor. It binds to E3 ligase ligands with weak binding affinities to VHL protein in the synthesis of PROTAC ARD-266.

Androgen receptor antagonist 1, an orally available full androgen receptor antagonist (IC50: 59 nM), is utilized in the synthesis of PROTAC AR degraders, achieving 24% and 47% AR protein degradation in LNCaP cells at concentrations of 1 μM and 10 μM, respectively.

PROTAC AR-NTD antagonist 1 (compound 18) is a small molecule from the protein-targeting chimeras (PROTACs) that selectively targets the N-terminal domain (AR-NTD) of the Androgen Receptor variant AR-V7. By antagonizing AR-NTD, it effectively degrades AR-V7 protein and induces apoptosis in prostate cancer (PC) cells, with degradation efficiencies of 62.2% (1 μM) and 71.1% (5 μM) in VCaP cells [1].

PROTAC AR-V7 degrader-1 (Compound 6) is an orally bioavailable, potent, and selective degrader targeting the androgen receptor (AR) variant V7, achieving degradation with a DC50 of 0.32 µM by directing the VHL E3 ligase to the AR DNA-binding domain (DBD). It demonstrates efficacy in the 22Rv1 cell line expressing AR-V7, with an EC50 of 0.88 µM [1].

CDK9 Antagonist-1 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1]. CDK9|17 μM (IC50, MCF-7 cells) [1]. Bian J , et al. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg Chem. 2018 Dec;81:373-381.