ar degrader-1

AR Degrader-1 (Compound ML 2-9) is a monovalent degrader of androgen receptors (AR) categorized under molecular glues. In LNCaP prostate cancer cells, it facilitates AR degradation through DCAF16 (E3 ligase) while exhibiting minimal cytotoxicity.

AR/BET protein degrader-1 (Compound 149) is a dual-targeting protein degrader of Androgen Receptor and BET (bromodomain and extra-terminal domain), suitable for cancer research.

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].

PROTAC AR/AR-V7 degrader-1 (27c) serves as a dual degrader targeting both AR and AR-V7, showcasing DC50 values of 2.67 and 2.64 μM for AR and AR-V7, respectively. It effectively induces apoptosis.

PROTAC RAR Degrader-1, an RAR degrader, consists of a cIAP1 ligand binding group, a linker, and an RAR ligand binding group. It achieves maximal RAR degradation at a concentration of 30 μM in HT1080 cells. Degradation inducers that utilize cIAP1 are known as specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

PROTACAR Degrader-10 is a protein degrader targeting androgen receptors (AR) with a DC50 value of ≤100 nM, and can be used in prostate cancer research.

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 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].

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].

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].

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).

5-Hydroxypentanoic acid is a PROTAC linker utilized in the synthesis of PROTAC AR-V7 degrader-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.

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].

α1A-AR Degrader 9c is a potent, selective, and reversible PROTAC degrader targeting the α1A adrenergic receptor (α1A-AR) with a DC50 of 2.86 μM. It promotes the proteasomal degradation of the α1A-AR and exhibits anti-proliferative effects against PC-3 cells, presenting an IC50 value of 6.12 μM. This compound demonstrates antitumor activity and holds potential for prostate cancer research [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].

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].