Halofuginone-hydrochloride-RU-19110-hydrochloride-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHalofuginonehydrochlorideCat.No.:HY-N1584BCASNo.:1217623-74-9Synonyms:RU-19110hydrochloride分?式:C??H??BrCl?N?O?分?量:451.14作?靶點(diǎn):CalciumChannel;DNA/RNASynthesis;Parasite;SodiumChannel;TGF-beta/Smad作?通路:MembraneTransporter/IonChannel;NeuronalSignaling;CellCycle/DNADamage;Anti-infection;StemCell/Wnt;TGF-beta/Smad儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Halofuginone(RU-19110)hydrobromid，F(xiàn)ebrifugine的衍?物，?種競(jìng)爭(zhēng)性的脯氨酰-tRNA合成酶(prolyl-tRNAsynthetase)抑制劑，Ki為18.3nM。HalofuginonehydrobromidI型膠原(type-Icollagen)合成的特異性抑制劑，并通過(guò)抑制TGF-β活性可減輕?關(guān)節(jié)炎。Halofuginonehydrobromid也?種有效的肺?管擴(kuò)張劑，可激活Kv通道并阻斷電壓門(mén)控、受體操作和存儲(chǔ)操作的Ca2+channels通道。Halofuginonehydrobromid具有抗瘧疾、抗炎、抗癌、抗纖維化作?。IC50&TargetKi:18.3±0.5nM(prolyl-tRNAsynthetase)[2]體外研究Halofuginonehydrobromidcompetitivelyinhibitsprolyl-tRNAsynthetasebyoccupyingboththeprolineandtRNA-bindingpocketsofprolyl-tRNAsynthetase[1].TheIC50sofHalofuginonehydrobromid(1,10,100,1000,10000nM;48hours)are114.6and58.9nMinKYSE70andA549cells,respectively[1].TheIC50sofHalofuginonehydrobromid(1,10,100,1000nM;24hours)forNRF2proteinare22.3and37.2nMinKYSE70andA549cells,respectively.TheIC50ofHalofuginoneforglobalproteinsynthesisis22.6and45.7nMinKYSE70andA549cells,respectively[1].Halofuginonehydrobromidincreasesvoltage-gatedK+(Kv)currentsinpulmonaryarterysmoothmusclecells(PASMC)andK+currentsthroughKCNA5channelsinHEKcellstransfectedwithKCNA5gene.Halofuginone(0.03-1μM)hydrobromidinhibitsreceptor-operatedCa2+entry(ROCE)inHEKcellstransfectedwithcalcium-sensingreceptorgeneandattenuatedstore-operated(SOCE)Ca2+entryin1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEPASMC[5].WesternBlotAnalysis[1]CellLine:KYSE70cellsfromhumanoesophagealcancerharbouringamutationintheNRF2geneandA549cellsharbouringtheKEAP1genemutation.Concentration:1,10,100,1000,10000nMIncubationTime:24hResult:TheIC50sforNRF2proteinwere22.3and37.2nMinKYSE70andA549cells,respectively.CellViabilityAssay[1]CellLine:KYSE70cellsfromhumanoesophagealcancerharbouringamutationintheNRF2geneandA549cellsharbouringtheKEAP1genemutationConcentration:1,10,100,1000,10000nMIncubationTime:48hResult:TheIC50swere114.6and58.9nMinKYSE70andA549cells,respectively.體內(nèi)研究Halofuginonehydrobromid(0.2,0.5,1or2.5mg/kg;injectedintraperitoneallyeveryotherdayfor1month)attenuatesprogressionofOAinanteriorcruciateligamenttransection(ACLT)mice.Lowerconcentration(0.2or0.5mg/kg)hasminimaleffectsonsubchondralboneandhigherconcentration(2.5mg/kg)inducesproteoglycanlossinarticularcartilage[3].Halofuginonehydrobromid(0.25mg/kg;intraperitoneallyinjected;everyday;16days)decreasesNRF2proteinlevelsintumors.Whilethetumorvolumesdonotchangesubstantiallybetweentreatmentswiththevehicle,Halofuginonehydrobromid(0.25mg/kg,intraperitoneallyinjected,everyday)orcisplatinalone.CombinedtreatmentwithHalofuginoneandCisplatinsignificantlysuppressesthetumorvolumecomparedtotreatmentwithHalofuginoneorcisplatinalone[1].IntraperitonealhydrobromidadministrationofHalofuginone(0.3mg/kg,for2weeks)partiallyreversestheestablishedpulmonaryhypertensioninmice[5].AnimalModel:3-month-oldmaleC57BL/6J(WT)mice[3]Dosage:0.2,0.5,1or2.5mg/kgAdministration:Injectedintraperitoneallyeveryotherdayfor1monthResult:AttenuatedprogressionofOAinACLTmice.AnimalModel:Malenudemice(BALB/Cnu/numice)(6-8-week)[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:0.25mg/kgAdministration:Intraperitoneallyinjected;everyday;16daysResult:ThecombinedtreatmentwithCisplatinsignificantlysuppressedthetumorvolume.NRF2proteinlevelsintumorswereindeeddecreased.REFERENCES[1].TsuchidaK,etal.Halofuginoneenhancesthechemo-sensitivityofcancercellsbysuppressingNRF2accumulation.FreeRadicBiolMed.2017Feb;103:236-247.[2].KellerTL,etal.HalofuginoneandotherFebrifuginederivativesinhibitprolyl-tRNAsynthetase.NatChemBiol.2012Feb12;8(3):311-7.[3].CuiZ,etal.HalofuginoneattenuatesosteoarthritisbyinhibitionofTGF-βactivityandH-typevesselformationinsubchondralbone.AnnRheumDis.2016Sep;75(9):1714-21.[4].TracyLMcGaha,etal.Halofuginone,aninhibitoroftype-Icollagensynthesisandskinsclerosis,blockstransforming-growth-factor-beta-mediatedSmad3activationinfibroblasts.JInvestDermatol.2002Mar;118(3):461-70.[5].PriteshPJain,etal.Halofuginone,aPromisingDrugforTreatmentofPulmonaryHyperte