Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETalmapimodCat.No.:HY-10406CASNo.:309913-83-5Synonyms:SCIO-469分?式:C??H??ClFN?O?分?量:513作?靶點(diǎn):p38MAPK作?通路:MAPK/ERKPathway儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(194.93mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9493mL9.7466mL19.4932mL5mM0.3899mL1.9493mL3.8986mL10mM0.1949mL0.9747mL1.9493mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(4.87mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.87mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.87mM);ClearsolutionBIOLOGICALACTIVITY?物活性Talmapimod(SCIO-469)p38α選擇性的，具有?服活性的，ATP競(jìng)爭(zhēng)性的抑制劑，IC50值9nM，約為p38β的10倍，在20個(gè)其他激酶(包括其他MAPKs)上顯?出?少2000倍的選擇性。IC50&Targetp38αp38β9nM(IC50)90nM(IC50)體外研究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.體內(nèi)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?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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