TargetValue hNNMT (Cell-free assay) 1.8 μM mkNNM (Cell-free assay) 2.8 μM mNNMT (Cell-free assay) 5.0 μM

JBSNF-000088 (6-Methoxynicotinamide) (50 mg/kg; oral route of administration for four weeks) shows statistically significant reduction in body weight (%) and leads to a statistically significant reduction in fed blood glucose on day 21. JBSNF-000088 (50 mg/kg; oral gavage administration; twice daily for four weeks) leads to a statistically significant improvement in oral glucose tolerance on day 28 with glucose tolerance being normalized. JBSNF-000088 (1 mg/kg; intravenous administration; for 4 hours) results in low plasma clearance of 21 mL/min▪kg and the volume of distribution at steady state of 0.7 L/kg, a very short plasma half-life of 0.5 hours upon intravenous administration. JBSNF-000088 (10 mg/kg; oral gavage; for 4 hours) results in a Cmax of 3568 ng/mL with a T max value of 0.5 hours, indicating rapid absorption in the intestine, and half-life of 0.4 hours by oral gavage. The oral bioavailability is found to be approximately 40%. Animal Model: Mice with high fat diet (HFD)-induced obesity Dosage: 50 mg/kg Administration: Oral route of administration for four weeks; oral gavage administration and twice daily for four weeks Result: Showed statistically significant reduction in body weight (%) and led to a statistically significant reduction in fed blood glucose on day 21 by oral route of administration. Led to a statistically significant improvement in oral glucose tolerance on day 28 with glucose tolerance being normalized by oral gavage administration. Animal Model: C57BL/6 mice Dosage: 1 mg/kg (Intravenous administration);10 mg/kg (oral gavage)(Pharmacokinetic Study) Administration: Intravenous administration and oral gavage; for 4 hours Result: Resulted in low plasma clearance of 21 mL/min▪kg and the volume of distribution at steady state of 0.7 L/kg, a very short plasma half-life of 0.5 h upon intravenous administration. Resulted in a Cmax of 3568 ng/mL with a T max value of 0.5 hours, indicating rapid absorption in the intestine, and half-life of 0.4 hours by oral gavage.

JBSNF-000088 (6-Methoxynicotinamide) has IC 50 values are 1.6 and 6.3 µM for U2OS or differentiated 3T3L1 cells.

JBSNF-000088 (6-Methoxynicotinamide)是一种 烟酰胺（NA）的类似物，是 Nicotinamide N-methyltransferase (NNMT) 的有效抑制剂，对 human NNMT(hNNMT)、monkey NNMT (mkNNMT) 和 mouse NNMT (mNNMT)的IC50值为1.8 µM、2.8 µM 和 5.0 µM。