Ravoxertinib-GDC-0994-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERavoxertinibCat.No.:HY-15947CASNo.:1453848-26-4Synonyms:GDC-0994分?式:C??H??ClFN?O?分?量:440.86作?靶點:ERK作?通路:MAPK/ERKPathway;StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥35mg/mL(79.39mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2683mL11.3415mL22.6829mL5mM0.4537mL2.2683mL4.5366mL10mM0.2268mL1.1341mL2.2683mL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。-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?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，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.67mg/mL(3.79mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.67mg/mL(3.79mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(3.79mM);Clearsolution4.請依序添加每種溶劑：30%PEG300>>70%(10%HP-β-CDinsaline)Solubility:5mg/mL(11.34mM);Clearsolution;Needultrasonic5.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.67mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ravoxertinib(GDC-0994)具有?服活性的ERK激酶抑制劑，抑制ERK1和ERK2的IC50分別為6.1nM和3.1nM。IC50&TargetERK1ERK2p-RSK6.1nM(IC50)3.1nM(IC50)12nM(IC50)體外研究Ravoxertinib(GDC-0994)alsoinhibitsp90RSKwithanIC50of12nM[1].Ravoxertinib(GDC-0994)ishighlyselectiveforERK1andERK2,withbiochemicalpotencyof1.1nMand0.3nM,respectively[2].Ravoxertinib(GDC0994;50nM,0.5μM,and5μM;48hours)decreasestheviabilityoflungadenocarcinomacelllines(A549,HCC827,HCC4006)[3].體內(nèi)研究InCD-1mice,a10mg/kgoraldoseofRavoxertinib(GDC-0994)issufficienttoachievethedesiredtargetcoverageforatleast8h[1].Daily,oraldosingofRavoxertinibresultsinsignificantsingle-agentactivityinmultipleinvivocancermodels,includingKRAS-mutantandBRAF-mutanthumanxenografttumorsinmice[2].PROTOCOLAnimalMice[1]Administration[1]PK/PDdataforRavoxertinib(GDC-0994)intheHCT116mousexenograftmodel.HCT116tumorsareestablishedinnudemicetoatumorvolumeof400-600mm3.Micearetreatedwithasingleoraldoseof22at15,30,or100mg/kgversusvehiclecontrolalone(40%PEG400/60%(10%HPβCD))followbytumorandplasmacollectionat2,8,16,and24hpostdose.Tumorlevelsofphosphorylatedp90RSK(pRSK)relativetotalp90RSK(tRSK)aremeasuredbyquantitativeWesternblotandarenormalizedtovehiclecontrolat2hpostdose(setto100%).PlasmaandtumorconcentrationsaremeasuredbyLC?MS.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻?Cell.2018Sep20;175(1):186-199.e19.?NatMetab.2022Mar;4(3):374-388.?SciTranslMed.2021Jan27;13(578):eaba7308.?NucleicAcidsRes.2022Apr8;50(6):3096-3114.?EnvironPollut.2021Jan1;268(PtB):115748.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BlakeJF,etal.Discoveryof(S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one(GDC-0994),anExtracellularSignal-RegulatedKinase1/2(ERK1/2)InhibitorinEarlyClinicalDevelopme[2].KirkRobarge,etal.AbstractDDT02-03:DiscoveryofGDC-0994,apotentandselectiveERK1/2inhibitorinearlyclinicaldevelopment.Proceedings:AACRAnnualMeeting2014;April5-9,2014.[3].MICHAELLAI.OpportunityforPharmaceuticalInterventioninLungCancer:SelectiveInhibitionofJAK1/2toEliminateEMT-DerivedMesenchymalCells.McePdfHeigh