Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors.

ABSTRACT

Methionine adenosyltransferase 2A (MAT2A) is a rate-limiting enzyme in the methionine cycle that primarily catalyzes the synthesis of S-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 MTAP 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.