Methionine adenosyltransferase 2A (MAT2A) has been indicated as a drug target for oncology indications. Clinical trials with MAT2A inhibitors are currently on-going. Here, a structure-based virtual screening campaign was performed on the commercially available chemical space which yielded two novel MAT2A-inhibitor chemical series. The binding modes of the compounds were confirmed with X-ray crystallography. Both series have acceptable physicochemical properties and show nanomolar activity in the biochemical MAT2A inhibition assay and single-digit micromolar activity in the proliferation assay (MTAP -/- cell line). The identified compounds and the relating structural data could be helpful in related drug discovery projects.

蛋氨酸腺苷转移酶 2A (MAT2A) 已被指定为肿瘤学适应症的药物靶点。MAT2A 抑制剂的临床试验目前正在进行中。在这里，在市售化学空间上进行了基于结构的虚拟筛选活动，产生了两种新型 MAT2A 抑制剂化学系列。通过X射线晶体学证实了化合物的结合模式。两个系列均具有可接受的理化性质，并在生化 MAT2A 抑制测定中显示纳摩尔活性，在增殖测定（MTAP -/- 细胞系）中显示个位数微摩尔活性。所鉴定的化合物和相关的结构数据可能有助于相关的药物发现项目。