メチオニンアデノシルトランスフェラーゼ2A阻害剤の軌跡：基礎研究から臨床試験後期まで

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Faridoon¹, Guiping Zhang¹

¹Center for Drug Design and Development, Suzhou Genhouse Bio Co., Ltd., Suzhou, Jiangsu 215123, China.

Journal of medicinal chemistry

|February 25, 2026

Abstract:

Methionine adenosyltransferase 2A (MAT2A) represents a promising target in precision oncology, especially for cancers with methylthioadenosine phosphorylase (MTAP) deletions. MAT2A inhibition induces synthetic lethality in MTAP-deleted cancers by depleting S-adenosylmethionine (SAM) and enhancing the inherent suppression of protein arginine methyltransferase 5 (PRMT5). Here, we trace the evolution of MAT2A inhibitors from early substrate-competitive molecules to allosteric inhibitors now in clinical evaluation. We discuss the design of next-generation inhibitors with improved potency, selectivity, and pharmacokinetic properties, including central nervous system penetration.

キーワード:

メチオニンアデノシルトランスフェラーゼ2A阻害剤 MTAP欠損癌精密腫瘍学合成致死性薬物発見

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