SB-431542-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemESB-431542Cat.No.:HY-10431CASNo.:301836-41-9分?式:C??H??N?O?分?量:384.39作?靶點:TGF-βReceptor作?通路:TGF-beta/Smad儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥40mg/mL(104.06mM)掃描?維碼，Ethanol:11.17mg/mL(29.06mM;Needultrasonicand運?溶解?案計算器warming)獲得適合您實驗體系的溶解?案*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6015mL13.0076mL26.0152mL5mM0.5203mL2.6015mL5.2030mL10mM0.2602mL1.3008mL2.6015mL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，并請注意儲備液的保存?式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(6.50mM);Clearsolution此?案可獲得≥2.5mg/mL(6.50mM，飽和度未知)的澄溶液。1/4www.MedChemEwww.MedChemE以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述2.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.50mM);Clearsolution此?案可獲得≥2.5mg/mL(6.50mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶液中，混合均勻。BIOLOGICALACTIVITY?物活性SB-431542?種有效，選擇性的ALK5/TGF-βtypeIReceptor抑制劑，IC50值為94nM。IC50&TargetALK594nM(IC50)體外研究SB-431542(1μM)significantlyreducestheTGF-β-inducednuclearaccumulationofSmadproteinsinA498cells.SB-431542inhibitsTGF-β1-inducedcollagenIα1andPAI-1mRNAwithIC50valuesof60and50nM,respectively.Inaddition,SB-431542inhibitsTGF-β1-inducedfibronectinmRNAandproteinwithIC50valuesof62and22nM,respectively[1].SB-431542(10μM)isaselectiveinhibitorofTGF-βsignalingbuthasnoeffectonBMPsignalinginNIH3T3cells[2].TRKI,SB-431542,inhibitsTGF-beta-inducedtranscription,geneexpression,apoptosis,andgrowthsuppression.SB-431542attenuatesthetumor-promotingeffectsofTGF-beta,includingTGF-beta-inducedEMT,cellmotility,migrationandinvasion,andvascularendothelialgrowthfactorsecretioninhumancancercelllines.SB-431542inducesanchorageindependentgrowthofcellsthataregrowth-inhibitedbyTGF-beta,whereasitreducescolonyformationbycellsthataregrowth-promotedbyTGF-beta[3].SB-431542(0.3μM)inhibitscellproliferationinducedbyTGF-βinMG63cells[4].體內(nèi)研究SB-431542(10mg/kg,i.p.)decreaseslungmetastasisbutdoesnotsignificantlyaltergrowthoftheprimarytumor4T1xenograft[5].PROTOCOLKinaseAssay[3]Atotalof100,000cellsfromeachpoolofA549andHT29areseededintoeachwellof12-wellplate.Cellsareculturedinmediacontaining0.2%FBSfor18hours,andthentreatedwith5ng/mLTGF-β1inthepresenceofSB-431542(10μM)in0.5mLofmediafor24hours.OnehundredμLsofeachsupernatantmediaisusedforVEGFassayaccordingtothemanufacturer'sinstruction.ForTGF-β1ELISA,100,000cellsfromeachpoolofA549,VMRC-LCD,andHT29areseededintoeachwellof12-wellplatesandserum-starvedfor20hours.CellsarethentreatedwithSB-431542in0.5mLofserum-freeRPMImediafor24hours.OnehundredμLsofeachsupernatantmediaisactivatedandusedforTGF-β1assayaccordingtothemanufacturer'sinstruction.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]A498cellsareseededat5,000to10,000cells/wellin96-wellplates.Thecellsareserum-deprivedfor24handthentreatedwithSB-431542for48htoassessthecellulartoxicity.Cellviabilityisdeterminedby2/4www.MedChemEwww.MedChemEincubatingcellsfor4hwithXTTlabelingandelectroncouplingreagentaccordingtothemanufacturer'sdirections.Livecellswithactivemitochondriaproduceanorange-coloredproduct,formazan,whichisdetectedusingaplatereaderatbetweenA450nmandA500nmwithareferencewavelengthgreaterthan600nm.Theabsorbancevaluescorrelatewiththenumberofviablecells.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalTenthousand4T1cellsareinjectedsubcutaneouslyintothesecondmammaryfatpadof6-week-oldBalb/cAdministration[5]femalemice.Tumorsaremeasuredtwiceweekly,andvolumeiscalculatedusingthefollowingformula:Volume=width2×length×0.52.Micearerandomlyassignedtotwotreatmentgroups:control,n=14(20%DMSO/80%cornoil);SB-431542-treated,n=15(10mg/kgbodyweightin20%DMSO/80%cornoil,administeredintraperitoneallythreetimesperweekstartingonedayaftertumorcellinoculation.Primarytumorsareresectedwhenthevolumeatday10post-injectionof4T1cells.Allmicearemonitoreddailyandeuthanizedafter4weeks.Themetastasesaredissectedtosnap-freezeforfurtheranalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?Small.2020Jun;16(22):e2001371.?Biomaterials.2020May;240:119849.?CancerRes.2020Oct15;80(20):4426-4438.?CancerRes.2019Sep1;79(17):4466-4479.?EMBOMolMed.2020Jan9;12(1):e10681.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].N.J.Laping,etal.InhibitionofTransformingGrowthFactor(TGF)-β1-InducedExtracellularMatrixwithaNovelInhibitoroftheTGF-βTypeIReceptorKinaseActivity:SB-431542.[2].InmanGJ,etal.SB-431542isapotentandspecificinhibitoroftransforminggrowthfactor-betasuperfamilytypeIreceptor-likekinase(ALK)receptorsALK4,ALK5,andALK7.MolPharmacol,2002,62(1),65-74.[3].HalderSK,etal.AspecificinhibitorofTGF-betareceptorkinase,SB-431542,asapotentantitumoragentforhumancancers.Neoplasia,2005,7(5),509-521.[4].MatsuyamaS,etal.SB-431542inhibitstransforminggrowthfactor-beta-inducedproliferationofhumanosteosarcomacells.CancerRes,2003,63(22),7791-7798.[5].SatoM,etal