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To increase aqueous solubility of the compounds to facilitate structural studies, the cycloheptyl substituent in TGR uncompetitive inhibitor 8 was replaced with a sugar moiety, resulting in compound 9 , a noncompetitive inhibitor and thus capable of binding the enzyme in absence of NADPH

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CB-839 is the most advanced GLS1 inhibitor currently in clinical practice and has been shown to effectively inhibit tumor proliferation ( L-asparaginase can deplete plasma Gln and is widely utilized as an adjuvant therapy in lymphoma ( In vitro experiments on lung cancer cells revealed that L-asparaginase treatment significantly induced autophagy activation in A549 cells, leading to their apoptosis ( 5 Discussion Metabolic reprogramming is essential for the advancement of tumors and has become a central topic in cancer research lately ( While substantial progress has been accomplished in the study of tumor Gln metabolism in recent years, several key issues remain to be addressed (1)

C., Pyzik, P

StructureActivity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase Journal of Medicinal Chemistry, 2017

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