Qi Chunchun, Yu Xinghui, Zuo Siyu, Han Pinsheng, An Ruonan, Zhang Yamin
School of Medicine, Nankai University, Tianjin 300071, China.
Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300071, China.
Molecules. 2025 May 12;30(10):2134. doi: 10.3390/molecules30102134.
The inhibition of methionine adenosyltransferase 2A (MAT2A) in cancers harboring deletions of the methylthioadenosine phosphorylase (MTAP) gene induces synthetic lethality, making it a highly compelling strategy in the pursuit of precision anticancer therapeutics. In this study, structure-based computing methods were employed to discover novel scaffolds as potential MAT2A inhibitors. The most potent compound, , demonstrated inhibition of MAT2A with an IC of 0.43 μM, and showed antitumor effects against MTAP HCT116 cells with an IC of 1.4 μM. The identified compounds and their associated structural data could provide valuable insights for related drug discovery projects.
在携带甲硫腺苷磷酸化酶（MTAP）基因缺失的癌症中，抑制甲硫氨酸腺苷转移酶2A（MAT2A）可诱导合成致死，这使其成为追求精准抗癌疗法的极具吸引力的策略。在本研究中，采用基于结构的计算方法来发现作为潜在MAT2A抑制剂的新型骨架。最有效的化合物，其对MAT2A的抑制IC50为0.43 μM，对MTAP缺失的HCT116细胞的IC50为1.4 μM，显示出抗肿瘤作用。所鉴定的化合物及其相关结构数据可为相关药物发现项目提供有价值的见解。
