SCH772984-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESCH772984Cat.No.:HY-50846CASNo.:942183-80-4分?式:C??H??N?O?分?量:587.67作?靶點(diǎn):ERK作?通路:MAPK/ERKPathway;StemCell/Wnt儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:48mg/mL(81.68mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7016mL8.5082mL17.0164mL5mM0.3403mL1.7016mL3.4033mL10mM0.1702mL0.8508mL1.7016mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.43mg/mL(2.43mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.43mg/mL(2.43mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.43mg/mL(2.43mM);Clearsolution4.請(qǐng)依序添加每種溶劑：20%SBE-β-CDadjustedtopH4-4.5with1NaceticSolubility:20mg/mL(34.03mM);Clearsolution;Needultrasonic5.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.4mg/mL(4.08mM);ClearsolutionBIOLOGICALACTIVITY?物活性SCH772984?種?選擇性和ATP競(jìng)爭(zhēng)性ERK抑制劑，對(duì)ERK1和ERK2的IC50分別為4和1nM。SCH772984在對(duì)天然MAPK抑制和耐藥MAPK抑制的細(xì)胞中的BRAF或RAS突變，具有抗腫瘤活性[1]。IC50&TargetERK2ERK11nM(IC50)4nM(IC50)體外研究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).體內(nèi)研究SCH772984(12.5-50mg/kg;i.p.;twicedailyfor14days)leadsto98%tumorregression[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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).戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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: