^
    3years
    [VIRTUAL] Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors (AACR 2021)
    In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow. In summary, we have used a fragment-based approach to discover a new class of orally active PRMT5•MTA inhibitors that demonstrate selective antitumor activity in MTAP-del tumor cells while sparing MTAP-WT cells.
    Late-breaking abstract • Synthetic lethality
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
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    CDKN2A deletion • MTAP deletion
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    MRTX9768