Rociletinib-CO-1686-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERociletinibCat.No.:HY-15729CASNo.:1374640-70-6Synonyms:CO-1686;AVL-301;CNX-419分⼦式:C₂₇H₂₈F₃N₇O₃分⼦量:555.55作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥43mg/mL(77.40mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8000mL9.0001mL18.0002mL5mM0.3600mL1.8000mL3.6000mL10mM0.1800mL0.9000mL1.8000mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.50mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Rociletinib(CO-1686)⼀种可⼝服的EGFR抑制剂，能够抑制EGFRL858R/T790M和EGFRWT的活性，IC50值分别为21.5nM和303.3nM。IC50&TargetEGFRL858R/T790MEGFRT790M21.5nM(Ki)303.3nM(Ki)体外研究Rociletinib(CO-1686)(0.1μM)inhibitsEGFRpotentlyandirreversibly,andinhibitsmorethan50%of23targets.RociletinibpotentlyandselectivelyinhibitsgrowthofNSCLCcellsexpressingmutantEGFRandinducesapoptosis.RociletinibresistantNSCLCcelllinesaresensitivetoAKTinhibition[1].体内研究Rociletinib(CO-1686)(100mg/kg/day,p.o.)demonstratesanti-tumoractivityinNSCLCEGFRmutantxenograftmodels.Rociletinib(CO-1686)(50mg/kgbid,p.o.)demonstratesanti-tumoractivityinhumanEGFR-L858RandEGFR-L858R-T790Mexpressingtransgenicmice[1].PROTOCOLCellAssay[1]Cellsareseededat3,000cells/wellingrowthmediasupplementedwith5%FBS,2mML-glutamine,and1%P/S,allowedtoadhereovernight,andtreatedwithadilutionseriesoftestcompound(Rociletinib)for72hr.CellviabilityisdeterminedbyCellTiterGloandresultsarerepresentedasbackground-subtractedrelativelightunitsnormalizedtoaDMSO-treatedcontrol.Growthinhibition(GI50)valuesaredeterminedbyGraphPadPrism5.04.Combinationindex(CI)dataisgeneratedusingCalcuSyn.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalBriefly,NCrnu/numicearesub-cutaneouslyimplantedwith1×107tumorcellsin50%Matrigel(injectionAdministration[1]volumeof0.2mL/mouse).Oncetumorsreached100-200mm3,Animalsaredosedwithcompounds(Rociletinib)asoutlined(N=10animals/gp).Briefly,LUM1686PDXtumorfragments,harvestedfromdonormice,areinoculatedintoBALB/cnudemice.Administrationoftestcompounds(Rociletinib(CO-1686))isinitiatedatameantumorsizeofapproximately160mm3.Tumorgrowthismonitoredovertimetodeterminetumorgrowthinhibitionoftheexperimentalagentvs.vehicle.Theendpointoftheexperimentisameantumorvolume(MTV)incontrolgroupof2000mm3.PercentTGIisdefinedasthedifferencebetweentheMTVofthedesignatedcontrolgroupandtheMTVofthedrug-treatedgroup,expressedasapercentageoftheMTVofthedesignatedcontrolgroup.Dataispresentedasmean±standarderrorofthemean(SEM).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•Science.2017Dec1;358(6367):eaan4368.•ActaPharmSinB.2020May;10(5):799-811.•JMedChem.2017Apr13;60(7):2944-2962.•MolCancerRes.2021Jun28.•MolCancerTher.2018Mar;17(3):603-613.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WalterAO,etal.Discoveryofamutant-selectivecovalentinhibitorofEGFRthatovercomesT790M-mediatedresistanceinNSCLC.CancerDiscov.2013Sep25.McePdfHe