SCH772984-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESCH772984Cat.No.:HY-50846CASNo.:942183-80-4分⼦式:C₃₃H₃₃N₉O₂分⼦量:587.67作⽤靶点:ERK作⽤通路:MAPK/ERKPathway;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:48mg/mL(81.68mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7016mL8.5082mL17.0164mL5mM0.3403mL1.7016mL3.4033mL10mM0.1702mL0.8508mL1.7016mL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%salineSolubility:≥1.43mg/mL(2.43mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.43mg/mL(2.43mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.43mg/mL(2.43mM);Clearsolution4.请依序添加每种溶剂：20%SBE-β-CDadjustedtopH4-4.5with1NaceticSolubility:20mg/mL(34.03mM);Clearsolution;Needultrasonic5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.4mg/mL(4.08mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SCH772984⼀种⾼选择性和ATP竞争性ERK抑制剂，对ERK1和ERK2的IC50分别为4和1nM。SCH772984在对天然MAPK抑制和耐药MAPK抑制的细胞中的BRAF或RAS突变，具有抗肿瘤活性[1]。IC50&TargetERK2ERK11nM(IC50)4nM(IC50)体外研究SCH772984(300nM;24-48hours)resultsinaG1arrestinSCH772984-sensitivemelanomacells[1].SCH772984(3-300nM;24hours)inhibitsERKandRSKphosphorylation[1].SCH772984showsEC50valueslessthan500nMinapproximately88%and49%ofBRAF-mutant(n=25)orRAS-mutant(n=35)tumorlines,respectively[1].CellCycleAnalysis[1]CellLine:LOXcells(SCH772984-sensitivemelanomacells)Concentration:300nMIncubationTime:24,48hoursResult:RevealedaG1arrestaswellasanincreaseinthesub-G1fractionindicativeofapoptosis.WesternBlotAnalysis[1]CellLine:LOXBRAFV600EmelanomacellsConcentration:3,10,30,100,300nMIncubationTime:24hoursResult:Adose-dependentinhibitionofphosphorylationoftheERKsubstrateRSK(T359/S363phospho-RSK),andalsoinhibitedphosphorylationofresiduesintheactivationloopofERKitself(T202/Y204andT185/Y187ofERK1andERK2,respectively).体内研究SCH772984(12.5-50mg/kg;i.p.;twicedailyfor14days)leadsto98%tumorregression[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDose-dependentantitumoractivityisalsoobservedintheKRAS-mutantpancreaticMiaPaCamodel,with36%regressionat50mg/kgtwicedaily.Importantly,tumorregressionisaccompaniedbyrobustinhibitionofERKphosphorylationintumortissue.SCH772984iswelltoleratedonthisscheduleasmeasuredbymorbidity,lethality,orbodyweightloss[1].AnimalModel:FemalenudemicebearinghumanLOXBRAFV600Etumors[1]Dosage:12.5,25,50mg/kgAdministration:Intraperitonealinjection;twicedailyfor14daysResult:Tumorregressionswereobservedatalldoses,suchas17%at12.5mg/kg,84%at25mg/kg,and98%at50mg/kg).户使⽤本产品发表的科研⽂献•Immunity.2021Sep14;54(9):2042-2056.e8.•NatNanotechnol.2021Jul;16(7):830-839.•NatCellBiol.2021Apr;23(4):377-390.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•DevCell.2021Dec20;56(24):3334-3348.e6.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MorrisEJ,etal.DiscoveryofanovelERKinhibitorwithactivityinmodelsofacquiredresistancetoBRAFandMEKinhibitors.CancerDiscov.2013Jul;3(7):742-50.McePdfHeightCaution: