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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/PCI-32765（同义词：伊布替尼）/HY-10997/500mg
商品详细Medchemexpress/PCI-32765（同义词：伊布替尼）/HY-10997/500mg
Medchemexpress/PCI-32765（同义词：伊布替尼）/HY-10997/500mg
Medchemexpress/PCI-32765（同义词：伊布替尼）/HY-10997/500mg
商品编号： HY-10997-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1320.00
美元价： 792.00
产地： 美国(厂家直采)
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产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
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商品介绍
PCI-32765isaselective,irreversIBLeBtkinhibitorwithIC50valueof0.5nM.

CustomerValidation

  • •Blood.2016Jun23;127(25):3237-52.
  • •Leukemia.2016Jan;30(1):173-81.
  • •MolCellProteomics.2012Jun;11(6):M112.017764.
  • •BrJHaematol.2015Jul;170(1):134-8.
  • •BrJHaematol.2015Mar;168(5):701-7.
  • •JExpClinCancerRes.2017Sep25;36(1):132.
  • •Oncotarget.2016Oct25;7(43):69760-69769.
  • •Oncotarget.2015Oct13;6(31):31313-22.
  • •SciRep.2017Mar28;7(1):466.
  • •SciRep.2014Dec23;4:7583.
  • •SignalTransductionandTargetedTherapy.27October2017.
  • •Patent.20170128439A1.
  • •Patent.US20170128439A1.
  • •Patent.US20160222465A1.
  • •HarvardMedicalSchoolLINCSLIBRARY
Description

PCI-32765isaselective,irreversibleBtkinhibitorwithIC50valueof0.5nM.

IC50&Target

IC50:0.5nM(Btk)

InVitro

PCI-32765selectivelyinhibitsB-cellsignalingandactivation.ItinhibitsautophosphorylationofBtk(IC50=11nM),phosphorylationofBtk"sphysiologicalsubstratePLCγ(IC50=29nM),andphosphorylationofafurtherdownstreamkinase,ERK(IC50=13nM)[1].PCI-32765inhibitsBCR-activatedprimaryBcellproliferation(IC50=8nM).FollowingFcγRstimulation,PCI-32765inhibitsTNFα,IL-1βandIL-6productioninprimarymonocytes(IC50=2.6,0.5,3.9nM,respectively)[3].

InVivo

PCI-32765(3.125-50mg/kg,p.o.)reducesthelevelofcirculatingautoantibodiesandcompletelysuppressesdiseaseinmicewithcollagen-inducedarthritis.PCI-32765inhibitsautoantibodyproductionandthedevelopmentofkidneydiseaseintheMRL-Fas(lpr)lupusmodel.PCI-32765(3.125-50mg/kg,p.o.)reducesrenaldiseaseandautoantibodyproductioninMRL-Fas(lpr)mice[1].PCI-32765(0.1μM)inhibitsactivation-inducedproliferationofCLLcells,inducesselectivecytotoxicityinBcellscomparedwithTcells,butaltersactivationinducedT-cellcytokineproduction[2].PCI-32765dose-dependentlyandpotentlyreversesarthriticinflammationinatherapeuticCIAmodelwithanED50of2.6mg/kg/day.PCI-32765alsopreventsclinicalarthritisinCAIAmodels[3].

ClinicalTrial
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References

  • [1].HonigbergLA,etal.TheBrutontyrosinekinaseinhibitorPCI-32765blocksB-cellactivationandisefficaciousinmodelsofautoimmunediseaseandB-cellmalignancy.ProcNatlAcadSciUSA.2010Jul20;107(29):13075-80.

    [2].HermanSE,etal.BrutontyrosinekinaserepresentsapromisingtherapeutictargetfortreatmentofchroniclymphocyticleukemiaandiseffectivelytargetedbyPCI-32765.Blood.2011Jun9;117(23):6287-96.

    [3].ChangBY,etal.TheBrutontyrosinekinaseinhibitorPCI-32765amelioratesautoimmunearthritisbyinhibitionofmultipleeffectorcells.ArthritisResTher.2011Jul13;13(4):R115.

    [4].WuH,etal.IrreversibleinhibitionofBTKkinasebyanovelhighlyselectiveinhibitorCHMFL-BTK-11suppressesinflammatoryresponseinrheumatoidarthritismodel.SciRep.2017Mar28;7(1):466.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.2701mL11.3507mL22.7015mL
5mM0.4540mL2.2701mL4.5403mL
10mM0.2270mL1.1351mL2.2701mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[3]

PCI-32765isdissolvedinDMSO.

PrimaryhumanBcellsareisolatedfromperipheralbloodmononuclearcellofhealthyhumanvolunteersbyFicoll-HypaquegrADIentseparationfollowedbynegativeselectionusinghumanMiltenylhumanBcellIsolationKitII.In0.2mLRPMIplus10%FBS,100,000BcellsaretreatedwithPCI-32765(0.3nM-10μM)intriplicatewellsorvehiclecontrolin0.1%DMSOfinalconcentrationfor30minutesat37°C,5%CO2,thencellsarestimulatedwith10μg/mLanti-IgMF(ab")2,5μg/mLanti-CD3/CD28asanegativecontrolor0.5μg/mLPMA(Phorbal12-myristate13-acetate)asapositivecontrol.Bcellsarestimulatedfor72hoursat37°C,5%CO2.ProliferationismeasuredwithCellTiterGloreagentandmeasuredonaluminometer.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[3]

CI-32765isformulatedin1%methylcellulose,0.4%Cremephor®EL,and98.09%water.

MaleDBA1/1OlaHsdmiceareinjectedondays0and21withFreunds"CompleteAdjuvantcontainingbovinetypeIIcollagen.Ondays21to35,micearerandomizedintotreatmentgroupswhentheaverageclinicalscoreofeachanimalis1.5(inascaleof5).PCI-32765treatment(1.56-12.5mg/kg,p.o.)isinitiatedfollowingenrollmentandcontinuesfor18days.Clinicalscoresaregiventoeachmousedailyforeachpaw.Clinicalscoreassessmentismadeusingthefollowingcriteria:0=normal;1=onehindpaworforepawjointaffectedorminimaldiffuseerythemaandswelling;2=twohindorforepawjointsaffectedormilddiffuseerythemaandswelling;3=threehindorforepawjointsaffectedormoderatediffuseerythemaandswelling;4=markeddiffuseerythemaandswellingorfourdigitjointsaffected;5=severediffuseerythemaandsevereswellingofentirepaw,unabletoflexdigits.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].HonigbergLA,etal.TheBrutontyrosinekinaseinhibitorPCI-32765blocksB-cellactivationandisefficaciousinmodelsofautoimmunediseaseandB-cellmalignancy.ProcNatlAcadSciUSA.2010Jul20;107(29):13075-80.

    [2].HermanSE,etal.BrutontyrosinekinaserepresentsapromisingtherapeutictargetfortreatmentofchroniclymphocyticleukemiaandiseffectivelytargetedbyPCI-32765.Blood.2011Jun9;117(23):6287-96.

    [3].ChangBY,etal.TheBrutontyrosinekinaseinhibitorPCI-32765amelioratesautoimmunearthritisbyinhibitionofmultipleeffectorcells.ArthritisResTher.2011Jul13;13(4):R115.

    [4].WuH,etal.IrreversibleinhibitionofBTKkinasebyanovelhighlyselectiveinhibitorCHMFL-BTK-11suppressesinflammatoryresponseinrheumatoidarthritismodel.SciRep.2017Mar28;7(1):466.

MolecularWeight

440.5

Formula

C₂₅H₂₄N₆O₂

CASNo.

936563-96-1

Storage

4°C,protectfromlight

Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥52mg/mL

PCI-32765isdissolvedinDMSOandthensUSPendedinnormalsaline(0.9%NaCl,NS)[4].

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

References

  • [1].HonigbergLA,etal.TheBrutontyrosinekinaseinhibitorPCI-32765blocksB-cellactivationandisefficaciousinmodelsofautoimmunediseaseandB-cellmalignancy.ProcNatlAcadSciUSA.2010Jul20;107(29):13075-80.

    [2].HermanSE,etal.BrutontyrosinekinaserepresentsapromisingtherapeutictargetfortreatmentofchroniclymphocyticleukemiaandiseffectivelytargetedbyPCI-32765.Blood.2011Jun9;117(23):6287-96.

    [3].ChangBY,etal.TheBrutontyrosinekinaseinhibitorPCI-32765amelioratesautoimmunearthritisbyinhibitionofmultipleeffectorcells.ArthritisResTher.2011Jul13;13(4):R115.

    [4].WuH,etal.IrreversibleinhibitionofBTKkinasebyanovelhighlyselectiveinhibitorCHMFL-BTK-11suppressesinflammatoryresponseinrheumatoidarthritismodel.SciRep.2017Mar28;7(1):466.

Purity:99.87%ee.:99.50%