Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETAK-715Cat.No.:HY-10456CASNo.:303162-79-0分?式:C??H??N?OS分?量:399.51作?靶點:p38MAPK;CaseinKinase作?通路:MAPK/ERKPathway;CellCycle/DNADamage;StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥100mg/mL(250.31mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5031mL12.5153mL25.0307mL5mM0.5006mL2.5031mL5.0061mL10mM0.2503mL1.2515mL2.5031mL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(fù)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。-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(dāng)?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(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(6.26mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.26mM);ClearsolutionBIOLOGICALACTIVITY?物活性TAK-715?種具有?服活性，有效的p38MAPK抑制劑，對p38α和p38β的IC50分別為7.1nM，200nM。TAK-715抑制酪蛋?激酶I(CK1δ/ε)，從?調(diào)節(jié)Wnt/β-catenin信號傳導(dǎo)的激活。TAK-715在??關(guān)節(jié)炎模型中顯?出良好的作?。IC50&Targetp38αp38βp38δp38γ7.1nM(IC50)200nM(IC50)>10μM(IC50)>10μM(IC50)CK1δCK1?體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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/?.ChemBiol,2011,18(4),485-494.[3].HuiwenRen,etal.Inhibitionofα1-adrenoceptorreducesTGF-β1-inducedepithelial-to-mesenchymaltransitionandattenuatesUUO-inducedrenalfibrosisinmice.FASEBJ.2020Nov;34(11):14892-14904.McePdfHeightCaution:Producthasnot