BIIB091-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBIIB091Cat.No.:HY-139984CASNo.:2247614-80-6分⼦式:C₂₈H₃₄N₁₀O₂分⼦量:542.64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:125mg/mL(230.36mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8428mL9.2142mL18.4284mL5mM0.3686mL1.8428mL3.6857mL10mM0.1843mL0.9214mL1.8428mL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:≥2.08mg/mL(3.83mM);Clearsolution1/2MasterofBioactiveMolecules—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:≥2.08mg/mL(3.83mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BIIB091⼀种有效，选择性，具有⼝服活性和可逆的BTK抑制剂，IC50值<0.5nM。BIIB091与BTK蛋⽩结合，将Tyr-551隔离成具有出⾊亲和⼒的⾮活性构象。BIIB091可⽤于多发性硬化症的研究。体外研究BIIB091inhibitsthephosphorylationofPLCγ2intheRamoshumanB-cellline,withanIC50of6.9nM[1].BIIB091blocksanti-IgM-stimulatedCD69activationinPBMCswithanIC50of6.9nM[1].BIIB091inhibitsFcγR-inducedROSproductioninpurifiedprimaryneutrophils,withanIC50of4.5nM[1].BIIB091inhibitsFcγRIandFcγRIII-mediatedTNFαsecretionuponsimulationwithFcγRagonistssuchascoatedhumanIgG(allFcγR,IC50=5.6nM),anti-CD16(FcγRIII,IC50=8.0nM),anti-CD64(FcγRIIC50=3.1nM),andcross-linkedanti-CD16(FcγRIIIIC50=1.3nM)inhumanmonocytes[1].BIIB091inhibitsthephosphorylationofBTK(IC50=24nM)andblocksbothBCRmediatedBcellandFcεR-inducedbasophilactivationasmeasuredbyinhibitionofCD69andCD63expression(IC50=71nMandIC50=82nM,respectively)inthewholebloodassays[1].体内研究BIIB091(0.03-30mg/kg;p.o.twicedailyfor10d)reducestheanti-NPIgMantibodytiters(88%,77%,59%,59%,44%,34%,and22%)intheTI-2immunizationmodel[1].PharmacokineticsofBIIB091inpreclinicalspecies[1]speciesIV(1mg/kg)PO(5mg/kg)inHMPC/TweenT1/2(h)AUCinf(h•ng/mL)CL(mL/min/kg)CL%QHVdss(L/kg)Tmax(h)Cmax(ng/mL)AUCinf(h•ng/mL)%Frat2.174810220.40.9693152242cyno1.194318440.70.331104144631dog6.0167512331.71.61440607589AnimalModel:C57BL/6miceimmunizedwithNP-Ficollathymus-independenttype2(TI-2)antigen[1]Dosage:0.03,0.1,0.3,1,10,30mg/kginaCMC/TweensuspensionformulationAdministration:P.o.twicedailyfor10daysResult:Observedasignificantreductionoftheanti-NPIgMantibodytiters(88%,77%,59%,59%,44%,34%,and22%).REFERENCES[1].HopkinsBT,etal.DiscoveryandPreclinicalCharacterizationofBIIB091,aReversible,SelectiveBTKInhibitorfortheTreatmentofMultipleSclerosis.JMedChem.2021Nov4.McePdfHeightCaution:Producthasnotbeenfullyvalidatedf