NNMTi 

NNMTi is a potent nicotinamide N-methyltransferase (NNMT) inhibitor (IC₅₀=1.2 μM) and selectively binds to the NNMT substrate-binding site residues^[2]. NNMTi  promotes myoblast differentiation in vitro and enhances fusion and regenerative capacity of muscle stem cells (muSCs) in aged mice^[1].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

286.11

Solid

C₁₀H₁₁IN₂

42464-96-0

C[N+]1=C2C=CC=C(N)C2=CC=C1.[I-]

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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]