Cobicistat-GS-9350-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECobicistatCat.No.:HY-10493CASNo.:1004316-88-4Synonyms:GS-9350分⼦式:C₄₀H₅₃N₇O₅S₂分⼦量:776.02作⽤靶点:CytochromeP450;HIV作⽤通路:MetabolicEnzyme/Protease;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(322.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.2886mL6.4431mL12.8863mL5mM0.2577mL1.2886mL2.5773mL10mM0.1289mL0.6443mL1.2886mL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:≥2.08mg/mL(2.68mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.68mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.68mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Cobicistat有效，选择性的细胞⾊素酶P4503A(CYP3A)抑制剂，IC50值为30-285nM。Cobicistat⼀种药代动⼒学增强剂，可增强抗HIV药物的吸收。IC50&TargetIC50:30-285nM(CytochromeP450)[1]体外研究InHIV-1proteaseenzymaticassayandantiviralcellularassays.CobicistatisinactiveagainstHIV-1protease(IC50>30μM).AndCobicistathasnoinhibitoryeffectagainstHIVreplicationinamulticycle5-dayMT-2HIVinfectionassay(EC50>30μM).InassaysusingMT-2cells,Cobicistatexhibitsminimalcytotoxicity,withaCC50valueabove80μM[1].ThemodeofinhibitionofhumanCYP3AbyCobicistatandRitonavirsharesthesamemechanismofactionfortheinhibitionofCYP3A.ItshowsitsinhibitoryeffectsonCYP3AmayinvolvedirectlyatthehemegroupoftheCYP3Aenzyme[1].TheminimaladverseeffectsofCobicistatintheseassayssuggestalowerpotentialfortoxicityrelatedtoalteredlipidmetabolism.Inthelipidaccumulationassaywiththehumanadipocytes,RitonavirshowsacleareffectwithanEC50of16μM.However,Cobicistatexhibitsnoeffectataconcentrationupto30μM[1].Intheglucoseuptakeassaywithmouseadipocytes,Ritonavirshowsapronouncedeffectattheconcentrationof10μM.Incontrast,theeffectsonglucoseuptakebyCobicistat(10μM)issignificantlyless[1].PROTOCOLKinaseAssay[1]InhibitionofhumancytochromeP450activitiesisdeterminedinduplicateinpooledhumanhepaticmicrosomalfractionsfollowingcurrentscientificandregulatoryguidelines.Reactionconditionsarelinearwithrespecttoincubationtimeandhepaticmicrosomalproteinconcentration.SubstratesarepresentatconcentrationsequaltoorlessthantheirrespectiveKmvaluesdeterminedunderthesamereactionconditions.Metaboliteand/orsubstrateconcentrationsaredeterminedusingspecific,internalstandardcontrolledHPLCMS/MSassays.Forreactionsmonitoringmetaboliteformationthereislessthan20%consumptionofsubstrateduringthereaction.Unlessotherwisenotedmicrosomalfraction,dilutedinpotassiumphosphatebuffer,ispreincubatedwithsubstrateandinhibitorfor5minat37°CandthereactioninitiatedbytheadditionofanNADPHgeneratingsystemfollowedbyfurtherincubationat37°Cwithshaking.Enzyme-selectivepositivecontrolinhibitorsaretestedinparallel.Atappropriatetimesaliquotsofthemixtureareremovedandthereactionterminatedbyadditiontoamixtureofmethanolandacetonitrilecontainingtherespectiveinternalstandard.AftercentrifugationaliquotsofthesupernatantaresubjectedtoHPLC-MS/MSanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellAssay[1]Five-foldserialdilutionsofthetestedcompoundsarepreparedintriplicatein96-wellplates.MT-2cellsareaddedtoplatesatadensityof20,000/wellinafinalassayvolumeof200μL.Aftera5-dayincubationat37°C,thecytotoxiceffectisdeterminedusingacellviabilityassay.OnehundredμLmediaisremovedfromeachwellandreplacedwith100μLofphosphate-bufferedsalinecontaining1.7mg/mLXTTand5μg/mLPMS.Following1-hourincubationat37°C,20μLof2%TritonX-100isaddedtoeachwellandabsorbanceisreadat450nmwithabackgroundsubtractionat650nm.Thedataareplottedascellviabilityvs.drugconcentration.Cellviabilityisexpressedasapercentageofthesignalfromuntreatedsamples(0%cytotoxicity)afterthesubtractionofsignalfromsamplestreatedwith10μMofPodophyllotoxin(100%cytotoxicity).TheCC50valueiscalculatedfromtheinhibitionplotsastheconcentrationofdrugwhichinhibitscellproliferationby50%.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•ActaPharmSinB.2021Mar22.•ActaPharmSinB.2020Aug.•EurJMedChem.2020Oct15;204:112626.•EurJMedChem.2020Aug15;200:112427.•Viruses.2020Apr16;12(4):452.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LianhongXu,etal.Cobicistat(GS-9350):APotentandSelectiveInhibitorofHumanCYP3AasaNovelPharmacoenhancer.ACSMed.Chem.Lett.,2010,1(5),pp209–213[2].TemesgenZ.Cobicistat,apharmacoenh