Discovery of the First-in-Class Protein Arginine Methyltransferase 1 PROTAC Degrader - PubMed
3 hours ago
- #PRMT1
- #PROTAC
- #Cancer Therapy
- Discovery of the first-in-class PROTAC degrader targeting PRMT1 (Protein Arginine Methyltransferase 1).
- Current PRMT1 modulators lack selectivity and rely on enzymatic inhibition.
- Compound 4, a PROTAC degrader, induces selective PRMT1 degradation in a concentration-, time-, and proteasome-dependent manner.
- High selectivity observed with no degradation of other common CRBN substrates or type I PRMTs.
- Compound 4 inhibits growth of multiple cancer cell lines and has a favorable pharmacokinetic profile.
- Molecular modeling suggests PRMT1 dimerization arm conformation promotes productive ternary complex formation with CRBN.
- Compound 4 serves as a valuable chemical tool for studying PRMT1 biology and its therapeutic potential in PRMT1-dependent cancers.