| Bioactivity | 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]. | ||||||||||||
| Target | IC50: 1.8 µM (human NNMT), 2.8 µM (monkey NNMT) and 5.0 µM (mouse NNMT) | ||||||||||||
| Invitro | 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 Tmax 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]. Animal Model: | ||||||||||||
| Name | JBSNF-000088 | ||||||||||||
| CAS | 7150-23-4 | ||||||||||||
| Formula | C7H8N2O2 | ||||||||||||
| Molar Mass | 152.15 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Kannt A, et al. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018 Feb 26;8(1):3660. |