NNMTi 是烟酰胺 N -甲基转移酶的抑制剂 (IC50=1.2 μM)，可选择性地结合 NNMT 底物结合位点残基。它能诱导体外成肌细胞分化，提高老年小鼠肌肉干细胞融合和再生能力。

NNMTi 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

NNMTi treatment will rescue age-related deficits in muSC activity to promote superior regeneration post-injury in aging muscle.?24-month old mice were treated with saline (control), and low and high dose NNMTi (5 and 10 mg/kg) for 1-week post-injury, or control and high dose NNMTi for 3-weeks post-injury.?All mice underwent an acute muscle injury (barium chloride injection) locally to the tibialis anterior (TA) muscle, and received 5-ethynyl-2'-deoxyuridine systemically to analyze muSC activity.?In vivo contractile function measurements were conducted on the injured TA muscle and tissues collected for ex-vivo analyses, including myofiber cross-sectional area (CSA) measurements to assess muscle recovery.?Results revealed that muscle stem cell proliferation and subsequent fusion were elevated in NNMTi-treated mice, supporting nearly 2-fold greater CSA and shifts in fiber size distribution to greater proportions of larger sized myofibers and fewer smaller sized fibers in NNMTi-treated mice compared to controls.?Prolonged NNMTi treatment post-injury further augmented myofiber regeneration evinced by increasingly larger fiber CSA.?Importantly, improved muSC activity translated not only to larger myofibers after injury but also to greater contractile function, with the peak torque of the TA increased by 70% in NNMTi-treated mice compared to controls.?Similar results were recapitulated in vitro with C2C12 myoblasts, where NNMTi treatment promoted and enhanced myoblast differentiation with supporting changes in the cellular NAD+/NADH redox states[1].

42464-96-0

C10H11IN2

286.11

5-Amino-1-methylquinolinium

DMSO:10 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years