castration-resistant prostate cancer

Bavdegalutamide (ARV-110) is an oral protein degrader that specifically binds to AR and mediates its degradation. Bavdegalutamide can degrade clinically relevant mutant AR proteins, maintain activity in a high androgen environment, and has an acceptable safety profile.

GDC-2992 is a selective and orally active androgen receptor (AR) degradator that degrades AR (DC50 = 2.7 nM) and inhibits proliferation (IC50 = 9.7 nM) in VCaP cells, making it suitable for studying castration-resistant prostate cancer (CRPC).

(S,R,S)-AHPC-Me dihydrochloride, also known as VHL ligand 2 dihydrochloride, is a chemical compound used in the synthesis of ARV-771. ARV-771 is a BET PROTAC degrader that relies on von Hippel-Landau (VHL) E3 ligase and exhibits potent degradation of BET proteins in castration-resistant prostate cancer (CRPC) cells, with a DC50 of less than 1 nM. This compound acts as the VHL ligand, specifically the (S,R,S)-AHPC-based VHL ligand, facilitating the recruitment of von Hippel-Lindau (VHL) protein.

EC1169 is a targeted tubulysin conjugate that utilizes EC1167 as its linker. This compound shows promise in the treatment of recurrent metastatic, castration-resistant prostate cancer (MCRPC)[1].

XYD049 (compound 7d) is a CRBN-type molecular glue targeting GSPT1, with a DC50 of 19 nM, used for researching MYC-driven castration-resistant prostate cancer (CRPC). It effectively inhibits the growth of 22Rv1 cells (IC50 = 7 nM) and exhibits antitumor efficacy in vivo. XYD049 downregulates CRPC-associated oncogenes in 22Rv1 cells, including AR, AR-v7, PSA, and c-Myc. XYD049 comprises a molecular glue linker (black part) NH2-C5-NH-Boc, a CRBN-type E3 ligase ligand (blue part) Thalidomide 4-fluoride, and a target protein ligand (red part) GSPT1 ligand-1, with the E3 ligase ligand + linker forming the conjugate E3 Ligase Ligand-linker Conjugate 158.

TD-802 (Compound 33c), an androgen receptor (AR) PROTAC degrader, exhibits strong microsomal stability and demonstrates potent antitumor efficacy in vivo, making it suitable for research on metastatic castration-resistant prostate cancer [1].

(S,R,S)-AHPC-Me (E3 ligase Ligand 1A) (VHL ligand 2) is an (S,R,S)-AHPC-based VHL ligand used to recruit the von Hippel-Lindau (VHL) protein. It is utilized in the synthesis of ARV-771, a VHL E3 ligase-based BET PROTAC degrader that effectively degrades BET proteins in castration-resistant prostate cancer (CRPC) cells with a DC50 <1 nM.