TAK-715-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETAK-715Cat.No.:HY-10456CASNo.:303162-79-0分⼦式:C₂₄H₂₁N₃OS分⼦量:399.51作⽤靶点:p38MAPK;CaseinKinase作⽤通路:MAPK/ERKPathway;CellCycle/DNADamage;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(250.31mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5031mL12.5153mL25.0307mL5mM0.5006mL2.5031mL5.0061mL10mM0.2503mL1.2515mL2.5031mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.26mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.26mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TAK-715⼀种具有⼝服活性，有效的p38MAPK抑制剂，对p38α和p38β的IC50分别为7.1nM，200nM。TAK-715抑制酪蛋⽩激酶I(CK1δ/ε)，从⽽调节Wnt/β-catenin信号传导的激活。TAK-715在⼤⿏关节炎模型中显⽰出良好的作⽤。IC50&Targetp38αp38βp38δp38γ7.1nM(IC50)200nM(IC50)>10μM(IC50)>10μM(IC50)CK1δCK1ϵ体外研究TAK-715(compound8h)inhibitsLPS-stimulatedreleaseofTNF-αfromTHP-1(IC50=48nM)andhasnoinhibitoryactivityformajorCYPs,includingCYP3A4.TAK-715hasnoinhibitiontop38γ/δ,JNK1,ERK1,IKKβ,MEKK1orTAK1(IC50>10μMofall)[1].TAK715(10μM;1hour)inhibitsWnt-3a-inducedhDvl2phosphorylationandthehDvl2shiftinU2OS-EFCcells[2].TAK-715(1μM;pretreatmentfor16hours)dramaticallysuppressesNorepinephrine(NE)-stimulatedinductionoffibronectin,CTGF,andSnai1expressioninTGF-β1-treatedHK-2cellsatboththemRNAandproteinlevels[3].体内研究TAK-715(compound8h;3-30mg/kg;PO)significantlyreducesthesecondarypawvolume[1].TAK-715(10mg/kg;PO)hasaCmaxof0.19μg/mLandanAUCof1.16μg•h/mL.AnimalModel:7-week-oldmaleLewisratswitharthritis[1]Dosage:3,10,30mg/kgAdministration:PO;singledoseResult:Significantlyreducedthesecondarypawvolume(25%inhibition)AnimalModel:Rat[1]Dosage:10mg/kg(PharmacokineticAnalysis)Administration:POResult:HadaCmaxof0.19μg/mLandanAUCof1.16μg•h/mL.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•JInvestDermatol.2019Jan;139(1):224-234.•FrontPharmacol.2018Jun21;9:660.•FASEBJ.2020Nov;34(11):14892-14904.•SciRep.2022Sep2;12(1):15001.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MiwatashiS,etal.Novelinhibitorofp38MAPkinaseasananti-TNF-alphadrug:discoveryofN-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide(TAK-715)asapotentandorallyactiveanti-rheumatoidarthritisagent.JMedChem,2005,[2].VerkaarF,etal.InhibitionofWnt/β-cateninsignalingbyp38MAPkinaseinhibitorsisexplainedbycross-reactivitywithcaseinkinaseIδ/ɛ.ChemBiol,2011,18(4),485-494.[3].HuiwenRen,etal.Inhibitionofα1-adrenoceptorreducesTGF-β1-inducedepithelial-to-mesenchymaltransitionandattenuatesUUO-inducedrenalfibrosisinmice.FASEBJ.2020Nov;34(11):14892-14904.McePdfHeightCaution:Producthasnot