JBSNF-000088

JBSNF-000088 (6-Methoxynicotinamide), a analog of nicotinamide (NA), is a potent and orally active Nicotinamide N-methyltransferase (NNMT) inhibitor with IC₅₀s of 1.8 µM, 2.8 µM, and 5.0 µM for human NNMT, monkey NNMT and mouse NNMT, respectively. JBSNF-000088 inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease^[1]. IC50 & Target:IC50: 1.8 µM (human NNMT), 2.8 µM (monkey NNMT) and 5.0 µM (mouse NNMT)^[1] In Vitro:JBSNF-000088 (6-Methoxynicotinamide) has IC₅₀ values are 1.6 and 6.3 µM for U2OS or differentiated 3T3L1 cells^[1]. In Vivo: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^[1].
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^[1].
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^[1].
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%^[1].