Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog–Thalidomide PROTACs
Ga Yeong Kim, Chae Won Song, Yo‐Sep Yang, Na-Rae Lee, Hyung-Seok Yoo, Seung Hwan Son, Soojin Lee, Jong Seon Park, Jong Kil Lee, Kyung‐Soo Inn, Nam‐Jung Kim
Abstract
A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.
Topics & Concepts
BicalutamideAndrogen receptorAndrogen Receptor AntagonistsProstate cancerChemistryDegradation (telecommunications)AndrogenCancer researchCombinatorial chemistryCancerBiologyInternal medicineBiochemistryMedicineComputer scienceHormoneTelecommunicationsProtein Degradation and InhibitorsMultiple Myeloma Research and TreatmentsUbiquitin and proteasome pathways