Spebrutinib-AVL-292-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESpebrutinibCat.No.:HY-18012CASNo.:1202757-89-8Synonyms:AVL-292;CC-292分⼦式:C₂₂H₂₂FN₅O₃分⼦量:423.44作⽤靶点:Btk作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥45mg/mL(106.27mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3616mL11.8080mL23.6161mL5mM0.4723mL2.3616mL4.7232mL10mM0.2362mL1.1808mL2.3616mL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(5.90mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.90mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Spebrutinib(AVL-292;CC-292)共价，⾼选择性和⼝服活性的Btk抑制剂，IC50为0.5nM。IC50&TargetIC50:[1]体外研究Spebrutinib(CC-292)isacovalent,highlyselective,orallyactiveinhibitorofBtkwithIC50valueof0.5nM.SpebrutinibalsolesspotentlyinhibitsYes,c-Src,Brk,Lyn,andFynwithIC50sof723nM,1.729μM,2.43μM,4.4μM,and7.15μM,rspectively.ExtensiveanalysishasrevealedthattheEC50ofBtkoccupancyfromaSpebrutinibdose-responseinRamoscells(EC50=6nM)correlateddirectlywiththecellularEC50ofBtkkinaseinhibitionwithSpebrutinib(EC50=8nM).Furthermore,theconcentrationatwhichSpebrutinibinhibits90%ofBtkactivityinRamoscellsis35nMwhiletheconcentrationofSpebrutinibrequiredfor90%occupancyofBtkis39nM[1].PROTOCOLCellAssay[1]Cellsareincubatedinserum-freeRPMImediafor1-1.5hours.IsolatedhumanBcellsareincubatedwithSpebrutinibatafinalconcentrationof0.001,0.01,0.1and1μM.Ramoscellsareincubatedwith0.1nM-3μMSpebrutinib.Cellsarethenincubatedinthepresenceofcompoundfor1hourat37°C.Followingincubation,cellsarecentrifugedandresuspendedin100μLofserum-freeRPMIandBCRisstimulatedwithadditionof5μg/mLα-humanIgM.Samplesarecentrifuged,washedinphosphate-bufferedsaline(PBS),andlysedin100μLofCellExtractionBufferplus1:10(v/v)PhosSTOPPhosphataseInhibitorand1:10(v/v)CompleteProteaseInhibitor.AntibodiesusedforimmunoblotanalysisincludeP-PLCγ2,PLCγ2(3871;CST),Syk(2712;CST),P-Syk(2710;CST),Btk,P-Btk,andTubulin.MembranesarescannedonaLi-CorOdysseyscannerusinginfraredfluorescencedetection[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Blood.2016Jun23;127(25):3237-52.•BrJPharmacol.2019Dec;176(23):4491-4509.•StemCellReports.2019May14;12(5):996-1006.•LeukRes.2020Jan;88:106286.•RSocOpenSci.2019Jun5;6(6):190434.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].EvansEK,etal.InhibitionofBtkwithCC-292providesearlypharmacodynamicassessmentofactivityinmiceandhumans.JPharmacolExpTher.2013Aug;346(2):219-28.McePdfHeightCaution:Producthasnotbee