JBSNF-000028 (JBSNF000028) is a potent, selective, orally bioavailable substrate-analog inhibitor of nicotinamide N-methyltransferase (NNMT) with IC50 of 34 nM, 190 and 210 nM against human, monkey and mouse NNMT, respectively.
JBSNF-000028 inhibits endogenous cellular NNMT activity in U2OS cells (24 h treatment) with EC50 of 2.5 uM by LCMS/MS detection.
JBSNF-000028 shows high selectivity in a panel of diabetes/obesity targets, receptor and ion channel panel, and shows no cytotoxicity in HepG2 cells at 100 uM.
JBSNF-000028 (50 mg/kg, b.i.d, p.o.) improveed glucose and lipid handling in mice with diet-induced obesity (DIO), demonstrated statistically significant reduction in body weight.
JBSNF-000028 (50 mg/kg, b.i.d, p.o.) showed statistically significant reduction in MNA levels in in genetic model of insulin resistance (ob/ob), with no reduction in fed blood glucose, insulin and plasma triglycerides, plasma total cholesterol, and plasma LDL cholesterol.