Vecabrutinib-SNS-062-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVecabrutinibCat.No.:HY-109078CASNo.:1510829-06-7Synonyms:SNS-062分?式:C??H??ClF?N?O?分?量:529.92作?靶點(diǎn):Btk;Itk作?通路:ProteinTyrosineKinase/RTK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:125mg/mL(235.88mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8871mL9.4354mL18.8708mL5mM0.3774mL1.8871mL3.7742mL10mM0.1887mL0.9435mL1.8871mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.93mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.93mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.93mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(4.72mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.72mM);ClearsolutionBIOLOGICALACTIVITY?物活性Vecabrutinib(SNS-062)?種有效的，?共價(jià)的BTK和ITK抑制劑，Kd值分別為0.3nM和2.2nM。Vecabrutinib對(duì)ITK的IC50值為24nM。IC50&TargetIC50:24nM(ITK)[2]Kd:0.3nM(BTK),2.2nM(ITK)[1]體外研究VecabrutinibinhibitspBTKinhumanwholebloodwithanaverageIC50of50nM.VecabrutinibinhibitsWTandC481SBTKwithsimilarIC50s(pBTKIC50s:WTBTK2.9nM,C481SBTK4.4nM)[1].Inarecombinantkinaseassay,IC50sofVecabrutinibagainstWTBTKandC481SBTKare4.6nMand1.1nM.VecabrutinibretainsactivityagainstthemutatedBTKvariant.VecabrutinibissixtimesmorepotentthanPCI-32765andgreaterthan640timesmorepotentthanacalabrutinibagainstC481SBTK.Vecabrutinibdemonstratesdose-dependentinhibitionofBTKinprimarypatientCLLcellscomparabletoPCI-32765viaimmunoblotforBTKphosphorylation.VecabrutinibdecreasesviabilityofprimaryCLLcellsinthepresenceofHS5stromalprotectionby5.5%[2].體內(nèi)研究Vecabrutinibhasgoodoralbioavailabilityinratanddog(%F≥40%)andaterminalhalf-lifeof5to6hours.VecabrutinibiswelltoleratedwithcontinuousdruglevelsandatexposuresmuchgreaterthanthoseachievedforPCI-32765[1].戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ProcNatlAcadSciUSA.2022Oct25;119(43):e2207280119.?JCIInsight.2019Jun20;4(12).pii:127566.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MinkeE.Binnerts,etal.AbstractC186:SNS-062isapotentnoncovalentBTKinhibitorwithcomparableactivityagainstwildtypeBTKandBTKwithanacquiredresistancemutation.MolecularCancerTherapeutics.December2015Volume14,Issue12Supplement2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[2].CatherineA.Fabian,etal.Abstract1207:SNS-062demonstratesefficacyinchroniclymphocyticleukemiainvitroandinhibitsC481SmutatedBrutontyrosinekinase.CancerResearchJuly2017Volume77,Issue13SupplementMcePdfHeightCaution:Producthasnotbeenfu