Tirabrutinib-hydrochloride-ONO-4059-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETirabrutinibhydrochlorideCat.No.:HY-15771ACASNo.:1439901-97-9Synonyms:ONO-4059hydrochloride;GS-4059hydrochloride分?式:C??H??ClN?O?分?量:490.94作?靶點:Btk;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(203.69mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0369mL10.1845mL20.3691mL5mM0.4074mL2.0369mL4.0738mL10mM0.2037mL1.0185mL2.0369mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.79mg/mL(3.65mM);Clearsolution1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.09mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.09mM);ClearsolutionBIOLOGICALACTIVITY?物活性Tirabrutinib(ONO-4059)hydrochloride?種?服有效的?選擇性Bruton’sTyrosineKinase(BTK)抑制劑(能透過?腦屏障)，其IC50值為6.8nM。Tirabrutinibhydrochloride不可逆共價結(jié)合BTK并抑制異常B細胞受體信號傳導。Tirabrutinibhydrochloride可?于??免疫性疾病和?液學惡性腫瘤的研究。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)體外研究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?邊的抑制劑?師www.MedChemEWesternBlotAnalysis[2]CellLine:TMD8cellsConcentration:300nMIncubationTime:72hResult:Inducedcaspase-3andPARPcleavage.體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻?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?邊的抑制劑?師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