甲硫氨酸腺苷转移酶2A（MAT2A）是催化S-腺苷甲硫氨酸（SAM）合成的关键酶，通过调控DNA、RNA及蛋白质的甲基化修饰，在表观遗传调控、细胞代谢及肿瘤发生发展中发挥重要作用。MAT2A在多种肿瘤中高表达，并与肿瘤增殖、转移及耐药密切相关。近年来，研究发现MAT2A与甲硫腺苷磷酸化酶（MTAP）基因缺失存在合成致死关系，该特异性效应可实现肿瘤选择性杀伤，使MAT2A成为MTAP缺陷型肿瘤精准治疗的重要靶点。目前多款MAT2A抑制剂已进入临床研究，其中IDE397推进至II期临床并展现出抗肿瘤潜力，国内多款候选药物亦进入I期临床评估。系统综述MAT2A的蛋白结构、生物学功能及其在肿瘤中的作用机制，重点总结MAT2A抑制剂的研究进展，包括临床分子以及探索阶段的多种类型的抑制剂，旨在为设计、开发安全有效的MAT2A抑制剂提供参考。

Methionine adenosyltransferase 2A (MAT2A) is a key enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM). By regulating the methylation modifications of DNA, RNA, and proteins, MAT2A plays an important role in epigenetic regulation, cellular metabolism, and tumor initiation and progression. MAT2A is highly expressed in various tumors and is closely associated with tumor proliferation, metastasis, and drug resistance. In recent years, numerous studies have uncovered a synthetic lethal interaction between MAT2A and methylthioadenosine phosphorylase (MTAP) gene deletion. Multiple MAT2A inhibitors have entered clinical trials, with IDE397 advancing to Phase II and several domestic candidates in Phase I. This review systematically summarizes the protein structure, biological functions, and mechanisms of action of MAT2A in tumors, with a focus on summarizing the research progress of MAT2A inhibitors, including clinical candidates and various types of inhibitors in the exploratory stage, aiming to provide a reference for the design and development of safe and effective MAT2A inhibitors.

R979.1