androgen receptor[1].

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.

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.

ARCC-4 is an enzalutamide-based von Hippel-Lindau (VHL)-recruiting AR PROTAC and outperforms enzalutamide and it is a low-nanomolar androgen receptor (AR) degrader based on PROTAC, with a DC50 of 5 nM. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy[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].

YT 6-2 analog-1 (compound 2-3) serves as an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, useful in synthesizing the AUTOTAC degrader ATC-324 for the Androgen Receptor (AR). ATC-324 promotes the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It effectively reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and can degrade common AR mutants found in prostate cancer (PCa).

Boc-Pip-alkyne-Ph-COOH, a PROTAC linker characterized by its alkyl ether composition, plays a crucial role in synthesizing PROTACs including ARD-266. This compound demonstrates significant efficacy in promoting the degradation of androgen receptor (AR) protein across AR-positive prostate cancer cell lines such as LNCaP, VCaP, and 22Rv1, showcasing DC50 values ranging from 0.2-1 nM[1].

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].

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].

VHL Ligand-Linker Conjugates 17 are chemical compounds that consist of a VHL ligand specialized for the E3 ubiquitin ligase, as well as a PROTAC linker. These conjugates are utilized in the synthesis of various PROTACs, including the notable ARD-266. ARD-266 is an exceptionally effective androgen receptor (AR) PROTAC degrader[1].

ARD-1676 is an orally administered androgen receptor (AR) PROTAC degrader that combines an AR ligand with a cereblon ligand. It demonstrates AR-degrading activity both in vitro and in vivo, and effectively inhibits VCaP tumor growth in mouse xenograft models [1].

PROTAC AR Degrader-4, an Androgen Receptor (AR) degrader, incorporates an IAP ligand binding group, a linker, and an AR binding group. It represents a class of degradation inducers known as specific and non-genetic IAP-dependent protein erasers (SNIPERs) [1], operating through a mechanism involving cIAP1.

cIAP1 ligand 1 (E3 ligase Ligand 12) is an apoptotic protein ligand based on the LCL161 derivative that recruits IAP ubiquitin ligases to degrade target proteins, and can be used in conjunction with androgen receptor ligands for the development of protein degradation agents that can be used in the study of prostate cancer.

VHL Ligand 8, a VHL ligand essential for synthesizing ARD-266, acts as a highly potent VHL E3 ligase-based androgen receptor (AR) PROTAC degrader. It efficiently facilitates the degradation of AR protein in AR-positive prostate cancer cell lines LNCaP, VCaP, and 22Rv1, exhibiting DC50 values ranging from 0.2-1 nM [1].

A031, a potent PROTAC androgen receptor (AR) degrader, demonstrates significant efficacy with an IC50 value under 0.25 μM for AR protein degradation. Additionally, it exhibits an inhibitory impact on tumor growth in zebrafish models of human prostate cancer (VCaP) [1].

ARD-2051 is a potent, orally active proteolysis-targeting chimera degrader of the androgen receptor (AR), exhibiting DC50 values of 0.6 nM in degrading AR protein within LNCaP and VCaP prostate cancer cell lines. It holds potential for prostate cancer research applications [1].