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| Product Name: | NNMTi | | Synonyms: | 5-amino-1-methylquinolin-1-ium iodide;5-amino-1MQ;NNMTi;5-Amino-1methylquinolinium iodide;5-Amino-1-methylquinolinium;NNMTi,inhibit,fusion,muSC,muscle stem cell,NNMT,Inhibitor,regenerative;NNMTi 5-amino-1MQ | | CAS: | 42464-96-0 | | MF: | | | MW: | 0 | | EINECS: | | | Product Categories: | API | | Mol File: | Mol File | ![NNMTi Structure]() |
| | NNMTi Chemical Properties |
| Melting point | 213-214 °C | | storage temp. | Store at -20°C | | solubility | Soluble in DMSO |
| | NNMTi Usage And Synthesis |
| Description | NNMTi is a nicotinamide N-methyltransferase (NNMT) inhibitor that promotes myoblast differentiation. NNMT is a fundamental cytosolic biotransforming enzyme that catalyzes the N-methylation of endogenous and exogenous xenobiotics. | | Biological Activity | NNMTi is a potent nicotinamide N-methyltransferase (NNMT) inhibitor (IC50=1.2 μM), selectively binding to NNMT substrate binding site residues. NNMTi can promote myoblast differentiation in vitro and enhance the fusion and regeneration of muscle stem cells in aged mice. | | in vitro | NNMTi (10-30 μM; 96 hours) produces a concentration-related increase in myoblast differentiation on C2C12 myoblast differentiation. 30 μM NNMTi results in 18% MHC-positive myotube nuclei, representing a 45% increase in the extent of myoblast differentiation compared to untreated differentiating myoblasts (12% MHC-positive myotube nuclei). | | in vivo | NNMTi (subcutaneous (SC) injection; 5 mg/kg and 10 mg/kg; 2 weeks (1 week pre-injury and 1 week post-injury)) has an effect on muscle regeneration after injury, it results in 60% and 75% higher incidence of proliferating/active muSCs at 5 mg/kg and 10 mg/kg, respectively. The relative numbers of fibers with an EdU + myonucleus increased 40% and 48% with NNMTi treatment at 5 mg/kg and 10 mg/kg, respectively. The odds ratio of fused myonuclei for control are 0.58 and 0.53 times the odds at the low and high NNMTi dose, respectively.NNMTi (subcutaneous injection; 10 mg/kg; 1 week) produces no systemic toxicity in mice, the levels of the glucose, cholesterol, plasma proteins, and electrolytes between control and NNMTi-treated samples show no difference in mice. 1-week post-injury daily repeat-dosing of NNMTi is well tolerated with no untoward systemic toxicity or behavioral implications in aged mice. | | storage | Store at -20°C | | 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. DOI:10.1016/j.bcp.2019.02.008
[2]. Harshini Neelakantan, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem DOI:10.1021/acs.jmedchem.7b00389
[3]. Mark A Eckert et al. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature, 569(7758), 723-728 (2019-05-03) DOI:10.1038/s41586-019-1173-8 |
| | NNMTi Preparation Products And Raw materials |
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