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    DRUG CLASS:

    MAT2A inhibitor

    Related drugs:
    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
    An Investigational Study of BG-89894 Tablets in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=140, Recruiting, BeiGene | Trial completion date: Dec 2026 --> Dec 2028
    Trial completion date
    6ms
    A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of SYH2039 Tablets in Adults with Advanced Solid Tumors (ChiCTR2500103521)
    P1, N=186, Recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci
    New P1 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    8ms
    Structure-Based Discovery of a Series of Novel MAT2a Inhibitors. (PubMed, ACS Med Chem Lett)
    Guided by the costructure of AZ-28 in complex with the MAT2a dimer, compound 9 was synthesized, demonstrating potent MAT2a inhibition (IC50 = 20 nM) and significantly enhanced antiproliferative activity (IC50 = 10 nM against HAP1MTAP-/- cells). Moreover, compound 9 exhibited improved selectivity compared to both AZ-28 and AG-270.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    S095033
    10ms
    Study of SYH2039 in Participants with Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=186, Recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    11ms
    Discovery of 2(1H)-Quinoxalinone Derivatives as Potent and Selective MAT2A Inhibitors for the Treatment of MTAP-Deficient Cancers. (PubMed, J Med Chem)
    Compound 28 also showed favorable pharmacokinetic properties and the improved in vivo anticancer activity in MTAP-deficient tumor models. These findings suggest new directions for the discovery and development of highly selective MAT2A inhibitors.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    11ms
    Discovery of Novel Spirocyclic MAT2A Inhibitors Demonstrating High In Vivo Efficacy in MTAP-Null Xenograft Models. (PubMed, J Med Chem)
    Both of these lead compounds demonstrate increased plasma drug exposure and exhibit significant efficacy in xenograft models that are depleted of MTAP. We hope that identifying a brain-penetrant MAT2A inhibitor will create new opportunities to explore the potential therapeutic effects of S-adenosylmethionine modulation in the central nervous system.
    Preclinical • Journal
    |
    MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    11ms
    Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=80, Recruiting, InSilico Medicine Hong Kong Limited | Not yet recruiting --> Recruiting
    Enrollment open
    1year
    SCR-7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with the S-adenosylmethionine-competitive or the methylthioadenosine-cooperative protein arginine methyltransferase 5 inhibitors in methylthioadenosine phosphorylase-deleted tumors. (PubMed, MedComm (2020))
    Different from AG-270, SCR-7952 exhibited little influence on metabolic enzymes and did not increase the plasma levels of bilirubin. The mechanism was via the aggravated inhibition of PRMT5 and FANCA splicing perturbations. These results indicated that SCR-7952 could be a potential therapeutic candidate for the treatment of MTAP-deleted cancers, both monotherapy and in combination with PRMT5 inhibitors.
    Journal • Combination therapy
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    MTAP (Methylthioadenosine Phosphorylase) • FANCA (FA Complementation Group A) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    MTAP deletion
    |
    S095033
    1year
    MAT2A inhibition combats metabolic and transcriptional reprogramming in cancer. (PubMed, Drug Discov Today)
    Thus, the pharmacological inhibition of MAT2A is emerging as a desirable therapeutic strategy to combat tumor growth. Here, we review the latest insights into MAT2A biology, focusing on its roles in both metabolic addiction and gene expression modulation in the TME, outline the current landscape of MAT2A inhibitors, and highlight the most recent clinical developments and opportunities for MAT2A inhibition as a novel anti-tumor therapy.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    over1year
    Study of SYH2039 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=186, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
    New P1 trial • Metastases