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NNMTi

MCE China：NNMTi

Brand：MedChemExpress (MCE)

Cat. No.HY-131042

CAS：42464-96-0

Purity：99.80%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：NNMTi is a potent nicotinamide N-methyltransferase (NNMT) inhibitor (IC50=1.2 μM) and selectively binds to the NNMT substrate-binding site residues. NNMTi promotes myoblast differentiation in vitro and enhances fusion and regenerative capacity of muscle stem cells (muSCs) 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)[1].

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[2].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[2].

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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.  [Content Brief]

[2]. Harshini Neelakantan, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem  [Content Brief]