在甲硫醇腺苷磷酸化酶（MTAP）缺乏的肿瘤细胞中，假设在高甲硫醇腺苷（MTA）情境下的还原型腺苷甲硫氨酸（SAM）水平会导致蛋白质精氨酸甲基转移酶5（PRMT5）的抑制和抑制肿瘤生长。甲硫氨酸腺苷转移酶2A（MAT2a）的抑制剂可以防止从甲硫氨酸合成SAM，因此在MTAP缺失性癌症中作为潜在的化学治疗药物吸引了越来越多关注。本文回顾了2018年1月至2021年12月之间的专利申请。评估了来自5个不同申请人的18个专利申请。该领域最近的进展表明MAT2a治疗假设得到了显著的关注。特别是Agios和Ideaya公司利用辉荧酰基结合模式，在此期间至少在两个申请中首次发表，开发出有效、选择性的抑制剂。他们已将MAT2a抑制剂推进到I期临床研究中，探讨其对患有MTAP缺失性实体肿瘤或淋巴瘤的患者的受益。虽然在此期间其他专利披露未公布候选药物，但Agios和Ideaya的研究将明确阐明此类抑制剂作为单一药物或联合用药作为可行治疗药物的潜力。

In methylthioadenosine phosphorylase (MTAP)-deficient tumor cells, reduced S-adenosylmethionine (SAM) levels in the context of elevated methylthioadenosine (MTA) has been hypothesized to lead to inhibition of protein arginine methyltransferase 5 (PRMT5) and tumor growth inhibition. Inhibitors of methionine adenosyltransferase 2A (MAT2a) prevent the synthesis of SAM from methionine and have therefore attracted increasing attention as potential chemotherapeutic agents in cancers characterized by MTAP-loss.This review covers patent applications between January 2018 and December 2021. 18 patent applications from 5 different applicants are evaluated.Recent advances in the field show a significant interest in the MAT2a therapeutic hypothesis. Agios and Ideaya in particular have capitalized on an allosteric binding mode first published by Pfizer in at least two of the filings during this time period, leading to potent, selective inhibitors. They have advanced MAT2a inhibitors to phase I clinical studies to explore their benefit to patients suffering with MTAP-deficient solid tumors or lymphoma. Whilst the other patent disclosures during this time frame have not led to disclosed candidates, the trials initiated by Agios and Ideaya studies will clearly inform on the potential for such inhibitors as viable therapeutic agents either as single agent or in combination.