NNMTi（CAS 42464-96-0 ）
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;1-methylquinolin-1-ium-5-amine iodide; promotes myoblast differentiation.
Appearance：Brown to brownish red powder
Purity：MIN99.0%
Test Method：HPLC
CAS No.: 42464-96-0
Molecular Formula:C10H11N2.I
Molecular Weight:286.11
EINECS: 464-196-0
Products Description
Description
NNMTi (CAS 42464-96-0) 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. NNMTi treatment combined with lean diet substitution accelerated improved body weight fat loss, increased whole-body lean mass to body weight ratio, reduced liver epididymal white adipose tissue weights, decreased liver adiposity, improved hepatic steatosis, relative to a lean diet substitution alone.
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Certificate of Analysis
|
Test Items |
Specifications |
Test Results |
|
Appearance |
Brown to brownish red powder |
Conforms |
|
Related substances |
Total impurities≤1.0% |
0.83% |
|
Purity(HPLC) |
≥99.0% |
99.17% |
|
Conclusion:Conforms to Enterprise standard |
||
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.
Solubility Data for NNMTi
Preparing Stock Solutions
Biological Functions
The cytosolic enzyme nicotinamide N-methyltransferase (NNMT) has been newly discovered to modulate the levels of nicotinamide precursors required for NAD+ biosynthesis and thus plays a crucial role in regulating the NAD+ salvage pathway and cellular metabolism. NNMT is expressed in skeletal muscle, with progressively greater expression associated with aging in muscle tissues. Importantly, NNMT is a dominant component of the gene expression signature for sarcopenia, overexpression of which could lead to significantly reduced levels of NAD+ and associated declines in muscle mass, strength, and function that accompany aging. Treatment of aged mice with a small molecule NNMT inhibitor (NNMTi) enhanced the proliferation, fusion, and regenerative capacity of muSCs, subsequently increasing the functional performance of skeletal muscle. Similar results were demonstrated in vitro with C2C12 cells that closely mimic muSCs, where NNMTi treatment promoted myoblast differentiation and supported metabolic changes in NAD+ salvage pathway-related cellular metabolites.
Applicaton
1.Research:
NNMTi is used to investigate NNMT's function in different biological contexts, including aging, muscle regeneration, and metabolic processes.
2.Muscle Regeneration:
NNMTi has shown promise in improving muscle regeneration in aged mice, enhancing the activity and regenerative capacity of muscle stem cells (muSCs).
3.Sarcopenia:
Research suggests that NNMTi can increase muscle strength and promote regeneration in aged muscle, offering a potential treatment for sarcopenia.
4.Obesity and Diabetes:
NNMTi has been shown to reverse diet-induced obesity and prevent associated type 2 diabetes (T2D).
5..Metabolic Diseases:
NNMTi may help restore normal metabolic function and address metabolic imbalances.
6.Heart Failure:
NNMT inhibition has been shown to improve cardiac function and reduce remodeling in heart failure models.
7. Food and health care products.
In essence, NNMTi is a tool for studying NNMT's role in various biological processes, with potential applications in treating age-related conditions, muscle diseases, obesity, diabetes, and potentially certain cancers.
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