^
    5ms
    MTA-Cooperative PRMT5 Inhibitors are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models. (PubMed, Clin Cancer Res)
    Clinical stage MTA-cooperative PRMT5 inhibitors TNG908 and TNG462 are efficacious in MPNST models in vitro and in vivo; therefore MTA-cooperative PRMT5 inhibitors are promising therapeutic agents for patients with MTAP-deleted MPNST.
    Preclinical • Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    TNG908 • vopimetostat (TNG462)
    6ms
    S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov)
    P1/2, N=308, Recruiting, Servier Bio-Innovation LLC | Phase classification: P1 --> P1/2 | N=27 --> 308 | Trial completion date: May 2026 --> Oct 2031 | Trial primary completion date: May 2026 --> Oct 2031
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    vopimetostat (TNG462)
    6ms
    Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Tango Therapeutics, Inc. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    daraxonrasib (RMC-6236) • zoldonrasib (RMC-9805) • vopimetostat (TNG462)
    8ms
    Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients (clinicaltrials.gov)
    P1/2, N=133, Not yet recruiting, Tango Therapeutics, Inc.
    New P1/2 trial
    |
    daraxonrasib (RMC-6236) • zoldonrasib (RMC-9805) • vopimetostat (TNG462)
    9ms
    Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with MTAP Deletion. (PubMed, J Med Chem)
    We have previously described the discovery of TNG908, a brain-penetrant clinical-stage compound that selectively targets MTAP-deleted cancer cells by binding to and inhibiting PRMT5 cooperatively with MTA, which is present in elevated concentrations in MTAP-deleted cells. Herein we describe the discovery of TNG462, a more potent and selective MTA-cooperative PRMT5 inhibitor with improved DMPK properties that is selective for MTAP-deleted cancers and is currently in Phase I/II clinical trials.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    TNG908 • vopimetostat (TNG462)
    12ms
    TNG462-C101: Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=225, Recruiting, Tango Therapeutics, Inc. | N=159 --> 225
    Enrollment change • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    Keytruda (pembrolizumab) • vopimetostat (TNG462)
    2years
    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
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    TNG908 • pemrametostat (GSK3326595) • vopimetostat (TNG462)
    over2years
    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
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    MTAP deletion
    |
    vopimetostat (TNG462)
    over2years
    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
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    vopimetostat (TNG462)
    almost3years
    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
    |
    vopimetostat (TNG462)