IPN60090-dihydrochloride-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIPN60090dihydrochlorideCat.No.:HY-103671ACASNo.:2102101-72-2分⼦式:C₂₄H₂₉Cl₂F₃N₈O₃分⼦量:605.44作⽤靶点:Glutaminase作⽤通路:MetabolicEnzyme/Protease储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:170mg/mL(280.79mM;Needultrasonic)H2O:100mg/mL(165.17mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6517mL8.2585mL16.5169mL5mM0.3303mL1.6517mL3.3034mL10mM0.1652mL0.8258mL1.6517mL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(sealedstorage,awayfrommoistureandlight)。-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%salineSolubility:≥5mg/mL(8.26mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥5mg/mL(8.26mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5mg/mL(8.26mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性IPN-60090dihydrochloride⼀种具有⼝服活性和⾼选择性的⾕氨酰胺酶1GLS1的抑制剂(IC50=31nM)，对GLS-2⽆活性。IPN-60090dihydrochloride在体内表现出优良的物理化学和药代动⼒学特性。IPN-60090dihydrochloride可⽤于实体肿瘤的研究，如肺癌和巢癌。IC50&TargetIC50:31nM(GLS1)[2]体外研究Therearetwoknownisoformsofglutaminase:GLS-1(alsocalledkidney-typeorKGA),andGLS-2(alsocalledliver-typeorLGA).GLS-1isubiquitousandGLS-2expressionappearslimitedprimarilytotheliver.Inadual-coupledenzymeassay,IPN60090dihydrochlorideinhibitspurifiedrecombinanthumanGLS-1(GACisoform)withanIC50of31nM,andhasnoactivityagainstGLS-2,withanIC50of>50000nM[2].IPN60090dihydrochlorideinhibitstheproliferationofA549cellswithanIC50of26nM[2].体内研究IPN60090dihydrochloride(3mg/kgfori.v.;10mg/kgforp.o.)hasexcellentpharmacokineticproperties,withCL=4.1mL/min/kg,t1/2=1hour,Cmax=19μM,F%=89%[2].IPN-60090dihydrochloride(oraladministration;100mg/kg;twicedaily;30days)showssimilarefficacyandtargetengagementtoCB-839(HY-12248)dosedorallyat250mg/kgtwicedaily.Andthe100mg/kgBIDdoseofIPN-60090isatolerateddoseforthefollowingmodelstudy[2].IPN-60090dihydrochloride(oraladministration;100mg/kg;twicedaily;30days;monotherapyorincombinationwithTAK228(HY-13328))causestumorgrowthinhibition.IPN-60090alonedemonstratesrobustinvivotargetengagementinadose-dependentmanner.Theglutamate/glutamineratiosandthefreeplasmaconcentrationsofIPN-60090at4hourspost-doseonbothday4andday28arealldecreased[2].Furthermore,IPN-60090dihydrochlorideincombinationwithTAK228stronglycausesan85%tumorgrowthinhibition,IPN-60090alonecausesa28%tumorgrowthinhibitioninvivo[2].AnimalModel:FemaleCD-1mice[2]Dosage:3mg/kgfori.v.;10mg/kgforp.o.(PharmacokineticAnalysis)Administration:IntravenousinjectionandoraladministrationResult:CL(4.1mL/min/kg),t1/2(1hour)fori.v.;Cmax(19μM),F%(89%)forp.o..AnimalModel:Ru337non-smallcelllungcancerpatient-derivedxenograft(PDX)subcutaneousmousemodelasmonotherapyorincombination[2]Dosage:100mg/kgAdministration:Oraladministration;100mg/kg;twicedaily;30days;monotherapyorincombinationwith2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemETAK228Result:Exhibitedanimprovementinthecombinationregimengroupovereithersingleagent.REFERENCES[1].MariaEmiliaDiFrancesco,etal.Gls1inhibitorsfortreatingdisease.WO2016004404A2.[2].MichaelJSoth,etal.DiscoveryofIPN60090,aClinicalStageSelectiveGlutaminase-1(GLS-1)InhibitorwithExcellentPharmacokineticandPhysicochemicalProperties.JMedChem.2020Nov12;63(21):12957-12977.McePdf