Glycodeoxycholic Acid is an endogenous metabolite, a natural product found in Streptomyces niger, Trypanosoma brucei, and Cryptomonas, which induces hepatocyte necrosis and autophagy in patients with obstructive cholestasis.

ARV-771, utilizing proteolysis-targeting chimera (PROTAC) technology, outperforms BET inhibitors in CRPC cellular models by effectively degrading BRD2/3/4 in 22Rv1 cells with a DC50 of less than 5 nM. This compound also significantly reduces c-MYC protein levels, a key BET protein effector, achieving an IC50 under 1 nM. Demonstrating potent anti-proliferative abilities, ARV-771 impacts 22Rv1, VCaP, and LnCaP95 cell lines, inducing apoptosis and altering cell morphology. Furthermore, treatment with 10 nM of ARV-771 notably suppresses FL-AR and AR-V7 mRNA in VCaP cells and exerts an antiandrogenic influence on several AR-regulated genes within these cells[1].

Administering daily subcutaneous injections of ARV-771 at a dosage of 10 mg/kg for three days to non-castrated male Nu/Nu mice with AR-V7+ 22Rv1 tumor xenografts resulted in a significant reduction of BRD4 and c-MYC levels in the tumor tissue by 37% and 76%, respectively. Additionally, a notable decrease in AR-V7 levels was observed in the 22Rv1 tumors following the treatment with ARV-771[1].