Tirabrutinib-hydrochloride-ONO-4059-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETirabrutinibhydrochlorideCat.No.:HY-15771ACASNo.:1439901-97-9Synonyms:ONO-4059hydrochloride;GS-4059hydrochloride分⼦式:C₂₅H₂₃ClN₆O₃分⼦量:490.94作⽤靶点:Btk;Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:100mg/mL(203.69mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0369mL10.1845mL20.3691mL5mM0.4074mL2.0369mL4.0738mL10mM0.2037mL1.0185mL2.0369mL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(sealedstorage,awayfrommoisture)。-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:≥1.79mg/mL(3.65mM);Clearsolution1/4MasterofBioactiveMolecules—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:2.5mg/mL(5.09mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.09mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tirabrutinib(ONO-4059)hydrochloride⼀种⼝服有效的⾼选择性Bruton’sTyrosineKinase(BTK)抑制剂(能透过⾎脑屏障)，其IC50值为6.8nM。Tirabrutinibhydrochloride不可逆共价结合BTK并抑制异常B细胞受体信号传导。Tirabrutinibhydrochloride可⽤于⾃⾝免疫性疾病和⾎液学恶性肿瘤的研究。IC50&TargetBMXBTKTECTXK6nM(IC50)6.8nM(IC50)48nM(IC50)92nM(IC50)BLKERBB4EGFRJAK30.3μM(IC50)0.77μM(IC50)3.02μM(IC50)5.52μM(IC50)ERBB27.31μM(IC50)体外研究Tirabrutinibhydrochloride(0.1-1000nMor0.001-100nM;72h)inhibitstheproliferationofOCI-LY10andSU-DHL-6cellswithIC50sof9.127nM,and17.10nM,respectively[1].Tirabrutinibhydrochloride(0.5,5,50μM;24,48h)inducesSU-DHL-6cellsapoptosisneedshighdosageandprolongedadministration(concentrationupto50μMandincubatesfor48h)[1].Tirabrutinibhydrochloride(300nM,72h)inducescaspase-3andPARPcleavageinTMD8cells[2].CellProliferationAssay[1]CellLine:SU-DHL-6andOCI-LY10cellsConcentration:0.1-1000nM;0.001nM-100nM.IncubationTime:72hResult:Showedgoodanti-proliferativeactivitywithIC50sof9.127nM,and17.10nMforOCI-LY10andSU-DHL-6cells,respectively.ApoptosisAnalysis[1]CellLine:SU-DHL-6cellsConcentration:0.5,5,50μMIncubationTime:24,48hResult:Inducedcellapoptosiswhenconcentrationupto50μMandincubatedfor48h.2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[2]CellLine:TMD8cellsConcentration:300nMIncubationTime:72hResult:Inducedcaspase-3andPARPcleavage.体内研究Tirabrutinibhydrochloride(10mg/kg;p.o.;single)israpidlyabsorbedintoplasmaandbrain,andreachesCmax(bloodCmax=339.53ng/mL;brainCmax=28.9ng/mL)2hourspostadministration[1].Tirabrutinibhydrochloride(6,20mg/kg;p.o.;singledailyfor3weeks)showsinhibitionoftumourgrowthinvivo[2].AnimalModel:MaleSDrats(219.0–260.5g)[1].Dosage:10mg/kgAdministration:Oraladministration;single.Result:1.19PharmacokineticParametersofTirabrutinibinmaleSDrats[1].Plasma,Cmax(ng/mL)Brain,Cmax(ng/mL)Penetrationrate(%,Cmax,brain/Cmax,plasma)PO(10mg/kg)339.5328.98.5AnimalModel:Immunodeficiency(SCID)mice(mousexenograftmodel)[2].Dosage:6,20mg/kgAdministration:Oraladministration;singledailyfor3weeks.Result:Inhibitedtumourgrowth,andwhendosageupto20mg/kg,acompletetumorsuppressionatday14.户使⽤本产品发表的科研⽂献•StemCellReports.2019May14;12(5):996-1006.•RapidCommunMassSpectrom.2021Dec14;e9240.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YuH,etal.Bruton'styrosinekinaseinhibitorsinprimarycentralnervoussystemlymphoma-evaluationofanti-tumorefficacyandbraindistribution.TranslCancerRes.2021May;10(5):1975-1983.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[2].KozakiR,etal.ResponsestotheSelectiveBruton'sTyrosineKinase(BTK)InhibitorTirabrutinib(ONO/GS-4059)inDiffuseLargeB-cellLymphomaCellLines.Cancers(Basel).2018Apr23;10(4):127.[3].LiclicanA,etal.BiochemicalcharacterizationoftirabrutinibandotherirreversibleinhibitorsofBruton'styrosinekinaserevealsdifferencesinon-andoff-targetinhibition.BiochimBiophysActaGenSubj.2020Apr;1864(4):129531.[4].DhillonS.Tirabrutinib:FirstApproval.Drugs