JBSNF-000028 is an orally active and potent nicotinamide N-methyltransferase (NNMT) inhibitor with inhibitory effects on human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT) with IC50s of 0.033 μM, 0.19 μM, and 0.21 μM, respectively.JBSNF-000028 can drive insulin sensitization and weight loss. 000028 drives insulin sensitization, glucose regulation and weight loss and can be used to study metabolic disorders.

U2OS cells:2.5 μM (EC50)

In U2OS cells, JBSNF-000028 hydrochloride (24 h) inhibits NNMT activity with an EC50 of 2.5 μM[1]. JBSNF-000028 hydrochloride (10-100 μM; 72 h) shows no cytotoxicity against HepG2 cells[1]. JBSNF-000028 hydrochloride binds below a hairpin structural motif at the nicotinamide pocket and stacks between Tyr-204 (from Hairpin) and Leu-164 (from the central domain)[1]. JBSNF-000028 hydrochloride is inactive against a broad panel of targets related to metabolism and safety[1].

In mice with diet-induced obesity (DIO), JBSNF-000028 hydrochloride (50 mg/kg; oral; twice daily for 27 days) improves glucose and lipid handling[1]. JBSNF-000028 hydrochloride (50 mg/kg; oral; twice daily for 4 weeks) improves glucose tolerance in NNMT knockout mice with diet-induced obesity[1].