Inhibition of methionine adenosyltransferase 2A (MAT2A) has received significant interest because of its implication as a synthetic lethal target in methylthioadenosine phosphorylase (MTAP)-deleted cancers. Here, we report the discovery of a series of 3-pyrido[1,2-]pyrimidin-3-one derivatives as novel MAT2A inhibitors. The selected compound exhibited high potency for MAT2A inhibition and a favorable pharmacokinetic profile. Furthermore, in an HCT-116 MTAP-deleted xenograft model, compound showed better potency than current clinical compound .
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726448 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.3c00488 | DOI Listing |
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