Talmapimod-SCIO-469-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETalmapimodCat.No.:HY-10406CASNo.:309913-83-5Synonyms:SCIO-469分⼦式:C₂₇H₃₀ClFN₄O₃分⼦量:513作⽤靶点:p38MAPK作⽤通路:MAPK/ERKPathway储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(194.93mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9493mL9.7466mL19.4932mL5mM0.3899mL1.9493mL3.8986mL10mM0.1949mL0.9747mL1.9493mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(4.87mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.87mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.87mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Talmapimod(SCIO-469)p38α选择性的，具有⼝服活性的，ATP竞争性的抑制剂，IC50值9nM，约为p38β的10倍，在20个其他激酶(包括其他MAPKs)上显⽰出⾄少2000倍的选择性。IC50&Targetp38αp38β9nM(IC50)90nM(IC50)体外研究Talmapimod(SCIO-469)(100-200nM;1hour)inhibitsphosphorylationofp38MAPKinMMcells[1].TalmapimodinhibitsLPS-inducedTNF-aproductioninhumanwholeblood[2].Talmapimoddecreasesconstitutivep38alphaMAPKphosphorylationofboth5T2MMand5T33MMcells[3].WesternBlotAnalysis[1]CellLine:MM.1S,U266,RPMI8226,MM.1R,andRPMI-Dox40celllinesConcentration:100,200nMIncubationTime:1hourResult:Stronglyinhibitsphosphorylationofp38MAPK.体内研究Targetingp38αMAPKwithTalmapimod(SCIO-469)decreasesmyelomaburdeninadditiontopreventingthedevelopmentofmyelomabonedisease[2].Talmapimodinhibitsmultiplemyelomagrowthandpreventsbonediseaseinthe5T2MMand5T33MMmodels[3].Talmapimod(10-90mg/kg;p.o.;twicedailyorallyfor14days)dose-dependentlyreducedtumorgrowthandalsodose-dependentlyreducedweightofthepalpabletumorsattermination[4].AnimalModel:Six-week-oldmaletripleimmune-deficientBNXmice(RPMI-8226MMpalpabletumors)[4]Dosage:P.o.;twicedailyorallyfor14daysAdministration:10,30,90mg/kgResult:Dose-dependentlyreducedtumorgrowth.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•Cell.2020Aug6;182(3):685-712.e19.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•CellBiolToxicol.2021Aug;37(4):515-529.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HideshimaTetal.p38MAPKinhibitionenhancesPS-341(bortezomib)-inducedcytotoxicityagainstmultiplemyelomacells.Oncogene.2004Nov18,23(54),8766-76.[2].VanderkerkenKetal.Inhibitionofp38alphamitogen-activatedproteinkinasepreventsthedevelopmentofosteolyticbonedisease,reducestumorburden,andincreasessurvivalinmurinemodelsofmultiplemyeloma.CancerRes.2007May15;67(10):4572-7.[3].NavasT,etal.Inhibitionofp38alphaMAPKdisruptsthepathologicalloopofproinflammatoryfactorproductioninthemyelodysplasticsyndromebonemarrowmicroenvironment.LeukLymphoma.2008Oct;49(10):1963-75.[4].MedicherlaS,etal.p38alpha-selectiveMAPkinaseinhibitorreducestumorgrowthinmousexenograftmodelsofmultiplemyeloma.AnticancerRes.2008Nov-Dec;28(6A):3827-33.McePdfHeightCaution:Producth