Definition

An orally bioavailable inhibitor of methionine adenosyltransferase II alpha (MAT2A), with potential antineoplastic activity. Upon oral administration, MAT2A inhibitor IDE397 targets, binds to and inhibits the activity of MAT2A, a metabolic enzyme responsible for the production of S-adenosyl-L-methionine (SAM), a primary donor of methyl groups in cellular transmethylation reactions that regulate gene expression, cell growth, and differentiation. Inhibition of MAT2A may inhibit proliferation in methylthioadenosine phosphorylase (MTAP)-deleted cancers that rely heavily on SAM synthesis. MAT2A activity is essential in cancer cells deficient in MTAP, a critical enzyme in the methionine salvage pathway, that is deleted in a variety of human cancers.