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    6ms
    MTA-cooperative PRMT5 inhibitors are efficacious in MTAP-deleted malignant peripheral nerve sheath tumor models (SNO 2023)
    The proliferation effects of MTA-cooperative PRMT5 inhibitors, TNG908 or TNG462, and a SAM-cooperative PRMT5 inhibitor, GSK3326595, on MTAP-deleted and MTAP-intact MPNST cell lines were determined using CellTiter-Glo (CTG) assays. The clinical stage MTA-cooperative PRMT5 inhibitors TNG908 (NCT05275478) and TNG462 (NCT05732831) are efficacious in MPNST models in vitro and in vivo and are therefore promising therapeutic agents for patients with MTAP-deleted MPNST.
    Preclinical
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    TNG908 • TNG462 • pemrametostat (GSK3326595)
    11ms
    Discovery of TNG462, a highly potent and selective MTA-cooperative PRMT5 inhibitor that is synthetic lethal for MTAP deleted cancers (ACS-Fall 2023)
    By binding to and inhibiting PRMT5 cooperatively with MTA, TNG462 leverages the synthetic lethal relationship between MTAP deletion and PRMT5 to selectively kill MTAP-deleted cells with a mean 45-fold selectivity over MTAP-proficient cells. Herein we report on the discovery of TNG462, a potential best-in-class, potent, and selective MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted cancer.
    Synthetic lethality
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    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
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    MTAP deletion
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    TNG462
    11ms
    Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=159, Recruiting, Tango Therapeutics, Inc. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    TNG462
    1year
    Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=159, Not yet recruiting, Tango Therapeutics, Inc.
    New P1/2 trial • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
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    TNG462