NNMTi

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NNMTi 是一种底物靶向、选择性烟酰胺 N-甲基转移酶 (NNMT) 抑制剂（IC50 = 1.2 μM；50 μM SAM、100 μM NCA），可降低 3T3-L1 脂肪生成 (EC50 = 30μM) 和脂肪细胞 1-甲基烟酰胺水平 (EC50) = 2.3 μM），而不影响 NAD+ 挽救途径中的相关甲基转移酶和酶。NNMTi 治疗将挽救与年龄相关的 muSC 活性缺陷，从而促进老化肌肉损伤后的卓越再生。

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 pathwayNNMTi 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.?

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5-Amino-1-methylquinolinium

Others

Other Targets

NNMT

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42464-96-0

286.11

C10H11IN2?

>98% (HPLC)

In Vitro:?DMSO : 20.83 mg/mL (72.80 mM)

[I-].C[n+]1cccc2c(N)cccc12

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(-20℃)

With Ice Pack

≥ 2 years