Tag: VHL

MS4322 is a First-in-Class PRMT5 PROTAC Degrader

PRMT5 is a member of type II protein arginine methyltransferases (PRMTs). When interacting with its binding partner MEP50, PRMT5 catalyzes monomethylation and symmetric dimethylation of arginine residues of its histone substrates. These substrates include H3R2, H3R8, and H4R3, and its nonhistone substrates, including p53, EGFR, N-MYC, SmD3, and RNA...

VZ185 is a Selective Dual BRD7/9 PROTAC Degrader

Targeted protein degradation is an emerging strategy to use small molecules to knock down a protein by hijacking the ubiquitin-proteasome system. PROTACs are bifunctional degrader molecules. They compose a ligand for the target protein and a ligand for E3 ligase recruitment, connected by a linker. An attractive feature of...

UNC6852 is a Selective Rolycomb Repressive Complex 2 (PRC2) PROTAC Degrader

Polycomb repressive complex 2 (PRC2) is a multicomponent complex with histone methyltransferase (HMT) activity. H3K27 trimethylation (H3K27me3) is a key mechanism responsible for gene repression. In this study, researchers report the discovery of an EED-targeted bivalent chemical degrader. Researchers show that UNC6852 potently binds EED in vitro, degrades EED...

ARCC-4 is a Highly Potent PROTAC Androgen Receptor Degrader

Androgen receptor (AR) signaling is crucial for normal prostate development. It also drives the growth and survival of prostate cancer cells. AR signaling suppression is a common strategy for treating prostate cancer. Like other occupancy-based inhibitors, the antiandrogen enzalutamide requires high saturating drug concentrations to achieve its clinical benefit....

PT2977 is an Orally Active and Selective HIF-2α Inhibitor for Solid Tumor Treatment

Previous studies have demonstrated that hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in clear cell renal cell carcinoma (ccRCC). PT2385 was the first reported HIF-2α inhibitor. However, PT2385 was restricted by variable and dose-limited pharmacokinetics. This results from extensive metabolism of PT2385 to its glucuronide metabolite. Herein,...