2-chloro-4-[trans-3-amino-2,2,4,4-tetramethylcyclobutoxy]benzonitrile

AR antagonist 1 (compound 29) is a potent androgen receptor (AR) antagonist and binds to E3 ligase ligands with weak binding affinities to VHL protein in the synthesis of PROTAC ARD-266 (HY-133020).

Research Areas >> Cancer

Signaling Pathways >> PROTAC >> Ligand for E3 Ligase

IC50: androgen receptor[1]

AR antagonist 1 (compound 29) is the ligand for target ligase of ARD-266. ARD-266 is a highly potent and VHL E3 ligase-based androgen receptor (AR) PROTAC degrader. AR antagonist 1 exhibits micromolar binding affinity to its E3 ligase complex, it can be successfully employed for the design of highly potent and efficient PROTAC degraders. PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins.

[1]. Han X, et al. Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. J Med Chem. 2019 Dec 26;62(24):11218-11231.