BTK-inhibitor-17-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBTKinhibitor17Cat.No.:HY-131705CASNo.:1858206-76-4分⼦式:C₂₅H₂₄N₆O₃分⼦量:456.5作⽤靶点:Btk作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(219.06mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1906mL10.9529mL21.9058mL5mM0.4381mL2.1906mL4.3812mL10mM0.2191mL1.0953mL2.1906mL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:≥2.5mg/mL(5.48mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.48mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.48mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BTKinhibitor17⼀种有效的具有⼝服活性不可逆BTK抑制剂，IC50为2.1nM。BTKinhibitor17可⽤于类风湿关节炎的研究。IC50&TargetIC50:2.1nM(BTK)[1]体外研究BTKinhibitor17(compound8)couldcovalentlybindtoCys481andformedanHBnetworkwithhingekeyresiduesMet477,Glu475,andgatekeeperThr474[1].体内研究BTKinhibitor17(compound8;3-10mg/kg;oralgavage;daily;for28days)treatmentinhibitsthesignificantprogressionofthediseaseandexhibitsacleardose-dependentreductionperpawclinicalscores,andnosignificantbodyweightlossisobservedforalldifferentdosages[1].BTKinhibitor17(compound8)shows>95%plasmaproteinbindingacrossthreespeciesofhuman,rat,andmouse.Afteranintravenousinjection,thehalf-life(rat,0.32h;mice,0.42h),clearance(rat,54.6mL/min/kg;mice,31.3mL/min/kg),volumeofdistribution(rat,1.55L/kg;mice,0.82L/kg),andAUCexposure(rat,604ng.h/mL;mice,576ng.h/mL)areobservedintwospecies.Afteroraladministration,BTKinhibitor17exhibitshigherCmax(rat,466ng/mL;mice,252ng/mL)andplasmaexposure(rat,642ng.h/mL;mice,128ng.h/mL)withafavorableoralbioavailability(rat,23.7%;mice,11.2%)[1].AnimalModel:MaleBalb/Cmiceinjectedwithcollagen[1]Dosage:3mg/kgor10mg/kgAdministration:Oralgavage;daily;for28daysResult:Inhibitedthesignificantprogressionofthediseaseandexhibitedacleardose-dependentreductionperpawclinicalscores.REFERENCES[1].XuejunZhang,etal.DiscoveryandEvaluationofPyrazolo[3,4-d]pyridazinoneasaPotentandOrallyActiveIrreversibleBTKInhibitor.ACSMedChemLett.2019Dec11;11(10):1863-1868.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical