| Chemical Properties | Back Directory | [Boiling point ]
283.9±50.0 °C(predicted) | [density ]
1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
13.83±0.20(predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
JBSNF-000028 is an orally active nicotinamide N-methyltransferase (NNMT) inhibitor with IC50s of 0.033 μM, 0.19 μM and 0.21 μM against human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT), respectively. JBSNF-000028 can be used for the research of metabolic disorders[1]. | [in vivo]
JBSNF-000028 (50 mg/kg; p.o.; twice daily for 27 days) improves glucose and lipid handling in mice with diet-induced obesity (DIO)[1].
JBSNF-000028 (50 mg/kg; p.o.; twice daily for 4 weeks) improves glucose tolerance in NNMT knockout mice with diet-induced obesity[1]. | Animal Model: | Male C57BL6/N mice, diet induced obesity (DIO) model[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration, b.i.d for 27 days | | Result: | Significantly reduced the body weight and fed blood glucose. Reduced 1-methyl-nicotinamide (MNA) levels in visceral WAT and liver. Led to a statistically significant reduction in plasma triglyceride, plasma LDL cholesterol, liver triglyceride and liver total cholesterol. |
| Animal Model: | Male C57BL6/N mice[1] | | Dosage: | 1 mg/kg and 10 mg/kg | | Administration: | Intravenous and oral administration (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic parameters of JBSNF-0000028 in mice following intravenous (1 mg/kg) and oral administration (10 mg/kg)[1].
| PK parameters | Intravenous | Oral | | Dose (mg/kg) | 1 | 10 | | AUC0–t (ng h/mL) | 446 | 1369 | | C0/Cmax (ng/mL) | 432 | 452 | | Tmax (h) | - | 1.00 | | T1/2 (h) | 1.77 | 2.36 | | Tlast (h) | 8.00 | 10.0 | | Cl (mL/min/kg) | 36.6 | - | | Vd (L/kg) | 8.69 | - | | F (%) | - | 30 |
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| [References]
[1] Ruf S, et al. Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2022 Sep 14;12(1):15440. DOI:10.1038/s41598-022-19634-2 |
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