Related Experiment Video
Updated: Feb 26, 2026

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Journey of Methionine Adenosyltransferase 2A Inhibitors: From Bench to Advanced Clinical Trials
1Center for Drug Design and Development, Suzhou Genhouse Bio Co., Ltd., Suzhou, Jiangsu 215123, China.
Abstract:
Methionine adenosyltransferase 2A (MAT2A) represents a promising target in precision oncology, especially for cancers with methylthioadenosine phosphorylase (MTAP) deletions. MAT2A inhibition induces synthetic lethality in MTAP-deleted cancers by depleting S-adenosylmethionine (SAM) and enhancing the inherent suppression of protein arginine methyltransferase 5 (PRMT5). Here, we trace the evolution of MAT2A inhibitors from early substrate-competitive molecules to allosteric inhibitors now in clinical evaluation. We discuss the design of next-generation inhibitors with improved potency, selectivity, and pharmacokinetic properties, including central nervous system penetration.
More Related Videos
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Clinical Trials: Overview
Preclinical Development: Overview
Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
Clinical Trials
There are four phases in a clinical trial. A phase one...

