| Description | NNMTi (5-Amino-1-methylquinolinium) is a substrate site-targeting, selective nicotinamide N-methyltransferase (NNMT) inhibitor (IC50 = 1.2 μM; 50 μM SAM, 100 μM NCA) that reduces 3T3-L1 lipogenesis (EC50 = 30μM) and adipocytes 1-methylnicotinamide level (EC50 = 2.3 μM) without affecting related methyltransferases & enzymes in the NAD+ salvage pathway |
| In vivo | NNMTi处理能够挽救老化肌肉干细胞(muSC)活性中与年龄相关的缺陷，从而在老化肌肉受伤后促进更优的再生。24个月大的老鼠在受伤后的第一周内接受了生理盐水(对照组)和低高剂量NNMTi（分别为5和10 mg/kg）治疗，或者在受伤后的3周内接受对照组和高剂量NNMTi治疗。所有小鼠都经历了急性肌肉损伤（局部注射氯化钡）至胫前肌(TA)并全身注射5-乙炔基-2'-脱氧尿苷以分析muSC活性。对受伤TA肌肉进行了体内收缩功能测量，并收集组织进行体外分析，包括测量肌纤维横截面积(CSA)以评估肌肉恢复。结果显示，与对照组相比，NNMTi处理的小鼠肌肉干细胞增殖及随后的融合提高，促使CSA几乎增加了2倍，并使纤维大小分布向较大纤维比例偏移，较小纤维比例减少。NNMTi治疗后期进一步增强了肌纤维再生，表现为越来越大的纤维CSA。重要的是，改善的muSC活性不仅表现为伤后较大的肌纤维，也表现为更强的收缩功能，与对照组相比，NNMTi处理的小鼠TA的峰值扭矩提高了70%。与C2C12肌母细胞体外试验获得的类似结果一致，NNMTi处理促进并增强了肌母细胞分化，并支持细胞内NAD+/NADH氧化还原状态的变化。 |
| Synonyms | 5-Amino-1-methylquinolinium |
| molecular weight | 286.11 |
| Molecular formula | C10H11IN2 |
| CAS | 42464-96-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 33.3 mg/mL (116.5 mM), Sonication is recommended. H2O: 33.3 mg/mL (116.5 mM), Sonication is recommended. |
| References | 1. Harshini Neelakantan, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019 May;163:481-492. 2. Benjamin Trinité, Hongtao Zhang, David N Levy ,et al.NNRTI-induced HIV-1 protease-mediated cytotoxicity induces rapid death of CD4 T cells during productive infection and latency reversal.Retrovirology. 2019 Jun 26;16(1):17. |