5-氨基-1-甲基喹啉-1-鎓碘化物

生物活性

NNMTi是一种有效的烟酰胺N-甲基转移酶(NNMT)的抑制剂(IC50=1.2μM)，可选择性地结合NNMT底物结合位点残基。NNMTi能促进体外成肌细胞分化，增强老年小鼠肌肉干细胞融合和再生能力。

体外研究

 NNMTi(10-30µM;96hours)producesaconcentration-relatedincreaseinmyoblastdifferentiationonC2C12myoblastdifferentiation.30µMNNMTiresultsin18%MHC-positivemyotubenuclei,representinga45%increaseintheextentofmyoblastdifferentiationcomparedtountreateddifferentiatingmyoblasts(12%MHC-positivemyotubenuclei).

体内研究

NNMTi(subcutaneous(SC)injection;5mg/kgand10mg/kg;2weeks(1weekpre-injuryand1weekpost-injury))hasaneffectonmuscleregenerationafterinjury,itresultsin60%and75%higherincidenceofproliferating/activemuSCsat5mg/kgand10mg/kg,respectively.TherelativenumbersoffiberswithanEdU+myonucleusincreased40%and48%withNNMTitreatmentat5mg/kgand10mg/kg,respectively.Theoddsratiooffusedmyonucleiforcontrolare0.58and0.53timestheoddsatthelowandhighNNMTidose,respectively.NNMTi(subcutaneousinjection;10mg/kg;1week)producesnosystemictoxicityinmice,thelevelsoftheglucose,cholesterol,plasmaproteins,andelectrolytesbetweencontrolandNNMTi-treatedsamplesshownodifferenceinmice.1-weekpost-injurydailyrepeat-dosingofNNMTiiswelltoleratedwithnountowardsystemictoxicityorbehavioralimplicationsinagedmice.