CC-115-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECC-115hydrochlorideCat.No.:HY-16962ACASNo.:1300118-55-1分⼦式:C₁₆H₁₇ClN₈O分⼦量:372.81作⽤靶点:DNA-PK;mTOR作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验H2O:50mg/mL(134.12mM;Needultrasonic)DMSO:≥30mg/mL(80.47mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6823mL13.4117mL26.8233mL5mM0.5365mL2.6823mL5.3647mL10mM0.2682mL1.3412mL2.6823mL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,awayfrommoisture)。-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：PBSSolubility:100mg/mL(268.23mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性CC-115hydrochloride⼀种有效的双重DNA-PK和mTOR抑制剂，IC50分别为13nM和21nM。CC-115阻断mTORC1和mTORC2信号通路。IC50&TargetDNA-PKmTORmTORC1mTORC213nM(IC50)21nM(IC50)PI3Kα852nM(IC50)体外研究CC-115inhibitsPC-3cellsproliferationwithanIC50of138nM.Inakinaseselectivityassessmentagainstapanelof250proteinkinasesat3μM,onlyonekinaseotherthanmTORkinaseisidentifiedwithmorethan50%inhibition(cFMS57%,IC50=2.0μM).OfthePI3Krelatedkinases(PIKKs)tested,CC-115provestobeequipotentagainstDNAPK(IC50=15nM)anddemonstrates40to>1000foldselectivityagainsttheremainingPIKKstested;PI3K-alpha(IC50=0.85μM),ATR(50%inhibitionat30μM)andATM(IC50>30μM).TheIC50valuesforCC-115are>10μMagainstapanelofCYPenzymesand>33μMforthehERG(humanether-a-go-go-relatedgene)ionchannel.Whenscreenedinasinglepointassayat10μMagainstaCerepreceptorandenzymepanelonlyonetargetisinhibited>50%(PDE3,IC50=0.63μM)[1].体内研究CC-115hydrochlorideshowsgoodinvivoPKprofilesacrossmultiplespecieswith53%,76%and~100%oralbioavailabilityinmouse,ratanddog,respectively.CC-115istestedatlowerdosesof0.25,0.5and1mg/kgbidor1mg/kgqd,withobservedcorrespondingtumorvolumereductionsof46%,57%,66%and57%respectively.CC-115sustainsinhibitionthough24hours.Atthe1mg/kgdoseCC-115showssignificantinhibitionat1and3hours,CC-115demonstratinginhibitionthrough10hours.CC-115isevaluatedusingbothonce(qd)andtwice(bid)dailydosingschedules[1].PROTOCOLKinaseAssay[1]AnHTR-FRETsubstratephosphorylationassayisemployedformTORkinase.PI3KαIC50determinationsareoutsourcedusingthemobilityshiftassayformat.Compounds(e.g.,CC-115)areassessedagainstconcentrationsofATPatapproximatelytheKmfortheassay,withaverageATPKmof15μMand50μMforthemTORandPI3Kassays,respectively[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]PC-3cellsareculturedingrowthmedia.Forbiomarkerstudiescellsaretreatedfor1handthenassayedforpS6andpAktlevelsusingMesoScaletechnology.Forproliferationexperiments,cellsaretreatedwithcompound(e.g.,CC-115)andthenallowedtogrowfor72h.AlldataarenormalizedandrepresentedasapercentageoftheDMSO-treatedcells.ResultsarethenexpressedasIC50values[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Encouragedbytheobservedexposures,CC-115isadvancedintosingledosePK/PDstudiesassessing2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEmTORpathwaybiomarkerinhibitionintumorbearingmice.PC-3tumor-bearingmiceareadministeredwithasingledoseofCC-115,dosedorallyateither1or10mg/kg,andplasmaandtumorsamplesarecollectedatvarioustimepointsforanalysis.SignificantinhibitionofbothmTORC1(pS6)andmTORC2(pAktS473)isobservedforallcompoundsandthelevelofbiomarkerinhibitioncorrelatedtoplasmacompoundlevels.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•FrontPharmacol.2020Nov11;11:580407.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MortensenDS,etal.OptimizationofaSeriesofTriazoleContainingMammalianTargetofRapamycin(mTOR)KinaseInhibitorsandtheDiscoveryofCC-115.JMedChem.2015