| Description | JBSNF-000028 is an orally active and potent nicotinamide N-methyltransferase (NNMT) inhibitor with inhibitory effects on human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT) with IC50s of 0.033 μM, 0.19 μM, and 0.21 μM, respectively.JBSNF-000028 can drive insulin sensitization and weight loss. 000028 drives insulin sensitization, glucose regulation and weight loss and can be used to study metabolic disorders. |
| In vitro | 在U2OS细胞中，JBSNF-000028 hydrochloride (24小时，EC50：2.5μM）抑制NNMT活性[1]。JBSNF-000028 hydrochloride (10-100μM；72小时)对HepG2细胞显示无细胞毒性[1]。JBSNF-000028 hydrochloride 位于烟酰胺口袋下的发夹结构动机，并在Tyr-204（来自发夹）和Leu-164（来自中心域）之间形成堆叠[1]。JBSNF-000028 hydrochloride 对与代谢和安全性相关的广泛靶标组无活性[1]。 |
| In vivo | 在饮食诱导的肥胖小鼠(DIO)中，JBSNF-000028 hydrochloride （50 mg/kg；口服；每天两次，持续27天）能改善葡萄糖和脂质代谢[1]。同样，JBSNF-000028 hydrochloride （50 mg/kg；口服；每天两次，为期4周）也能提高饮食诱导的肥胖的NNMT基因敲除小鼠的葡萄糖耐受性[1]。 |
| Target activity | U2OS cells:2.5 μM (EC50) |
| Synonyms | JBSNF-000028 free base |
| molecular weight | 187.24 |
| Molecular formula | C11H13N3 |
| Storage | |Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 3.85 mg/mL (20.54 mM), Sonication is recommended. |
| 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. |