Department of Pharmaceutical Engineering, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.
J Med Chem. 2022 Jul 28;65(14):9531-9547. doi: 10.1021/acs.jmedchem.2c00395. Epub 2022 Jul 7.
Methionine adenosyltransferase 2A (MAT2A) is a rate-limiting enzyme in the methionine cycle that primarily catalyzes the synthesis of -adenosylmethionine (SAM) from methionine and adenosine triphosphate (ATP). MAT2A has been recognized as a therapeutic target for the treatment of cancers. Recently, a few MAT2A inhibitors have been reported, and three entered clinical trials to treat solid tumorsor lymphoma with loss. This review aims to summarize the current understanding of the roles of MAT2A in cancer and the discovery of MAT2A inhibitors. Furthermore, a perspective on the use of MAT2A inhibitors for the treatment of cancer is also discussed. We hope to provide guidance for future drug design and optimization via analysis of the binding modes of known MAT2A inhibitors.
蛋氨酸腺苷转移酶 2A（MAT2A）是甲硫氨酸循环中的限速酶，主要催化从蛋氨酸和三磷酸腺苷（ATP）合成 S-腺苷甲硫氨酸（SAM）。MAT2A 已被认为是癌症治疗的一个治疗靶点。最近，有报道称有几种 MAT2A 抑制剂，其中三种进入临床试验，用于治疗伴有缺失的实体瘤或淋巴瘤。本综述旨在总结 MAT2A 在癌症中的作用及其抑制剂的发现。此外，还讨论了使用 MAT2A 抑制剂治疗癌症的前景。我们希望通过分析已知 MAT2A 抑制剂的结合模式，为未来的药物设计和优化提供指导。
