TNG456

TNG456 is a next-generation, brain-penetrant small molecule inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) designed for the precision treatment of cancers with methylthioadenosine phosphorylase (MTAP) deletion. Developed by Tango Therapeutics, TNG456 utilizes an MTA-cooperative mechanism of action, selectively binding to the PRMT5-MTA complex that accumulates specifically in MTAP-deleted tumor cells, thereby sparing healthy tissues. This selectivity results in a significantly wider therapeutic window compared to first-generation PRMT5 inhibitors. In preclinical models, the compound demonstrated high potency and the ability to cross the blood-brain barrier, making it a candidate for primary and metastatic central nervous system malignancies. It is currently under clinical evaluation as a monotherapy and in combination with the CDK4/6 inhibitor abemaciclib for patients with MTAP-deleted solid tumors, including glioblastoma and non-small cell lung cancer.

Other names

TNG456TNG-456TNG 456