IPN60090-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

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?靶點:Glutaminase作?通路:MetabolicEnzyme/Protease儲存?式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實驗DMSO:170mg/mL(280.79mM;Needultrasonic)H2O:100mg/mL(165.17mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6517mL8.2585mL16.5169mL5mM0.3303mL1.6517mL3.3034mL10mM0.1652mL0.8258mL1.6517mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(8.26mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥5mg/mL(8.26mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5mg/mL(8.26mM);ClearsolutionBIOLOGICALACTIVITY?物活性IPN-60090dihydrochloride?種具有?服活性和?選擇性的?氨酰胺酶1GLS1的抑制劑(IC50=31nM)，對GLS-2?活性。IPN-60090dihydrochloride在體內(nèi)表現(xiàn)出優(yōu)良的物理化學(xué)和藥代動?學(xué)特性。IPN-60090dihydrochloride可?于實體腫瘤的研究，如肺癌和巢癌。IC50&TargetIC50:31nM(GLS1)[2]體外研究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].體內(nèi)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?邊的抑制劑?師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