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Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIPN60090dihydrochlorideCat.No.:HY-103671ACASNo.:2102101-72-2分?式:C??H??Cl?F?N?O?分?量:605.44作?靶点:Glutaminase作?通路:MetabolicEnzyme/Protease储存?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;?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?式和期限:-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C储存时,请在6个?内使?,-20°C储存时,请在1个?内使?。体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照InVitro?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?作液,建议您现?现配,当天使?;以下溶剂前显?的百分?指该溶剂在您配制终溶液中的体积占?;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?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?边的抑制剂?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?物活性IPN-60090dihydrochloride?种具有?服活性和?选择性的?氨酰胺酶1GLS1的抑制剂(IC50=31nM),对GLS-2?活性。IPN-60090dihydrochloride在体内表现出优良的物理化学和药代动?学特性。IPN-60090dihydrochloride可?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?边的抑制剂?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.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuseonly.Tel:400-820-3792ax-mail:tech@MedChemE3/3MasterofBioactiveMolecules—您?边的抑制剂?师

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