Computer-aided design of a fluorescent MAT2A inhibitor for visualized cancer synthetic lethality

• Compound 3 N -h is a 26 nM MAT2A inhibitor, has yellow fluorescence, and can visualize MAT2A. • MAT2A inhibitor 3 N -h strongly inhibited the proliferation of MTAP-/- HCT-116 cells, but were almost non-toxic to wild-type HCT-116 cells. • The capability of 3 N -h in visualized cancer synthetic lethality was also validated in mice. • These features make 3 N -h extremely intriguing in accurate cancer diagnosis and therapy.