Molidustat-BAY-85-3934-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMolidustatCat.No.:HY-12654CASNo.:1154028-82-6Synonyms:BAY85-3934分⼦式:C₁₃H₁₄N₈O₂分⼦量:314.3作⽤靶点:HIF/HIFProlyl-Hydroxylase作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:5mg/mL(15.91mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.1817mL15.9084mL31.8167mL5mM0.6363mL3.1817mL6.3633mL10mM0.3182mL1.5908mL3.1817mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥0.5mg/mL(1.59mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥0.5mg/mL(1.59mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.5mg/mL(1.59mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Molidustat⼀种新型的HIF-PH抑制剂，对PHD1,PHD2,PHD3的IC50值分别为480nM,280nM和450nM。IC50&TargetIC50:480nM(PHD1),280nM(PHD2),450nM(PHD3)[1]体外研究ThemeanIC50valuesofBAY85-3934forPHD1,PHD2,andPHD3are480nM,280nM,and450nM,respectively.ExposureofHeLacellsto5μMBAY85-3934for20minissufficienttoinducedetectableconcentrationsofHIF-1α.Inacellularreporterassay,BAY85-3934inducestheexpressionofthefireflyluciferasereportergeneunderthecontrolofahypoxiaresponsiveelementpromoteratamean(±SD)EC50of8.4±0.7μM(n=4)[1].体内研究HIFstabilizationbyoraladministrationoftheHIF-PHinhibitorBAY85-3934(molidustat)resultsindose-dependentproductionofEPOinhealthyWistarratsandcynomolgusmonkeys.Molidustattherapyisaldoeffectiveinthetreatmentofrenalanemiainratswithimpairedkidneyfunctionand,unliketreatmentwithrhEPO,resultedinnormalizationofhypertensivebloodpressureinaratmodelofCKD[1].PROTOCOLAnimalRats:BAY85-3934ispreparedasasolutioninethanol:SolutolHS15:water(10:20:70).Inarepeat-dose,26-Administration[1]dayexperiment,maleWistarrats(240–340ginbodyweight)areadministeredvehicleorBAY85-3934atdosesof0.5mg/kg,1.25mg/kg,2.5mg/kg,and5mg/kg.TheefficacyofBAY85-3934(2.5mg/kg,once-daily,oral)isalsocomparedwiththatofrhEPO(25IU/kg,50IU/kg,and100IU/kg,twice-weekly,s.c.injection).Thetime-courseofinductionofEPOmRNAexpressionandplasmaEPOisdeterminedatbaselineand0.5h,1h,2h,4h,6h,and8hafteroraladministrationofasingledoseofBAY85-3934(5mg/kg)[1].Monkey:BAY85-3934ispreparedasasolutionin0.5%tylose.Maleandfemalecynomolgusmonkeys(2.8–5.6kginbodyweight)areadministeredatdosesof0.5mg/kgand1.5mg/kgat0h,24h,48h,72h,and96h.Bloodsamplesaretakenat7h,31h,55h,79h,103h,and168h.Erythropoieticparametersarealsoevaluatedaftera2-weektreatmentperiodwiths.c.administrationofrhEPO(100IU/kgtwiceweeklyatdays1,4,8,and11)andBAY85-3934(1.5mg/kg)oncedaily[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•iScience.21September2021.•JPharmaceutBiomed.2020,113870.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•BiochemBiophysResCommun.2018Sep3;503(1):297-303.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FlammeI,etal.Mimickinghypoxiatotreatanemia:HIF-stabilizerBAY85-3934(Molidustat)stimulateserythropoietinproductionwithouthypertensiveeffects.PLoSOne.2014Nov13;9(11):e111838.McePdfHeightCau