Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELeuRS-IN-1hydrochlorideCat.No.:HY-139987ACASNo.:1364683-67-9分?式:C??H??BCl?NO?分?量:277.94作?靶點:Bacterial作?通路:Anti-infection儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性LeuRS-IN-1hydrochloride?種有效的?服活性結核分枝桿leucyl-tRNA合成酶(M.tbLeuRS)抑制劑。LeuRS-IN-1hydrochloride對M.tbLeuRS的IC50和Kd值分別為0.06μM和0.075μM[1]。LeuRS-IN-1hydrochloride抑制?細胞質LeuRS(IC50=38.8μM)和HepG2蛋?合成(EC50=19.6μM)[2]。IC50&TargetM.tbLeuRSM.tbLeuRShumancytoplasmicHepG2protein0.06μM(IC50)0.075μM(Kd)LeuRSsynthesis38.8μM(IC50)19.6μM(EC50)體外研究LeuRS-IN-1(compound13)hydrochloridehasaMICvalueof0.02μg/mLforM.tbH37Rvbacteria[1].LeuRS-IN-1(compound3a)(48h)hydrochlorideinducesHepG2celltoxicitywithanEC50valueof65.8μM[2].體內研究LeuRS-IN-1(100mg/kg;orallydailyfor14days)hydrochloridereduceslungCFUvalueinacutetuberculosis(TB)mice[1].LeuRS-IN-1(33mg/kg;orally5daysaweekfor4weeks)hydrochloridereduceslungandspleenCFUvaluesinchronicTBmice[1].Murinepharmacokineticparameters[1]:AdministrationDose(mg/kg)Cmax(μg/ml)at5minCL(ml/h/kg)Vss(ml/kg)MRT(h)AUC0-∞(h·μg/ml)α-t1/2(h)(%AUC)β-t1/2(h)(%AUC)i.v.3013.65823,1425.451.60.10(2)3.83(98)AdministrationDose(mg/kg)Cmax(μg/ml)Tmax(h)AUC0-241/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE(h·μg/ml)Terminalt1/2(h)Bioavailability(%)(h·μg/ml)MousePPB(%)p.o.306.40.2523AnimalModel:MurineGKO(C57BL/6-Ifngtm1ts)modelofacuteTB[1]Dosage:100mg/kgAdministration:Orallydailyfor14daysafter10daysofinfection(start)withM.tuberculosisErdman.Result:ReducedlungCFUvalueinmice.AnimalModel:MurineBALB/cmodelofchronicTBinfection[1]Dosage:33mg/kgAdministration:Orally5daysaweekfor4weeksafterinfectionwithM.tuberculosisErdmanwithalow-doseaerosol21daysprior(start).Result:ReducedlungandspleenCFUvaluesinmice.REFERENCES[1].PalenciaA,etal.DiscoveryofNovelOralProteinSynthesisInhibitorsofMycobacteriumtuberculosisThatTargetLeucyl-tRNASynthetase.AntimicrobAgentsChemother.2016;60(10):6271-6280.Published2016Sep23.[2].LiX,etal.DiscoveryofaPotentandSpecificM.tuberculosisLeucyl-tRNASynthetaseInhibitor:(S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol(GSK656).JMedChem.2017Oct12;60(19):8011-8026.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.