Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEC188-9Cat.No.:HY-112288CASNo.:432001-19-9Synonyms:TTI-101分?式:C??H??NO?S分?量:471.52作?靶點(diǎn):STAT;Apoptosis作?通路:JAK/STATSignaling;StemCell/Wnt;Apoptosis儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:25mg/mL(53.02mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1208mL10.6040mL21.2080mL5mM0.4242mL2.1208mL4.2416mL10mM0.2121mL1.0604mL2.1208mL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(protectfromlight)。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.41mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性C188-9(TTI-101)Stat3的抑制劑，其Kd值為4.7nM。C188-9抑制G-CSF誘導(dǎo)的STAT3激活和STAT3依賴性因表達(dá)。C188-9誘導(dǎo)AML細(xì)胞系和原代標(biāo)本凋亡，抑制原代AML細(xì)胞集落形成。IC50&TargetSTAT34.7nM(Kd)體外研究C188-9isaStat3inhibitor,withaKdof4.7nM[1].TheIC50sofC188-9toinhibitStat3activationinAMLcelllinesareintherangeof4-7μM,andinprimaryAMLsamplestheIC50sareintherangeof8-18μM.Forapoptosisstudies,AMLcelllinesandprimarysamplesaretreatedfor24hourswithC188-9,thenapoptoticcellsarequantifiedbyFACSanalysisforannexinV-labeledcells.TheEC50sforapoptosisinductionarequitevariable,rangingfrom6μMtoover50μM[2].體內(nèi)研究Oftheapproximately13,528discerniblegenes,levelsof37genetranscriptsarealteredbyC188(17downand20up-regulated,fdr[3].PROTOCOLCellAssay[1]Celllinesareplatedat2to5×105cells/mLingrowthmediumandtreatedwithincreasingdosesofinhibitorfor24hours.CD34+AMLcellsareplatedat1to2×105cells/mLinIMDMwith20%FBSandPen/Strep,andincubatedwithC188-9(0.3to100μM)for48hours.Cellsarethenharvestedandlabeled.Thefractionofspontaneousapoptosisisdeterminedfromanuntreatedsampleandthensubtractedfromthedrug-treatedsamplestoyieldthepercentageofapoptosisattributedtodrugtreatment[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]UM-SCC-17Bcells(1.5×106)areinjectedintothetonguesofathymic,8-10weekold,male,nudemice.Oncetumorsareestablished,mice(20total;10/group)arerandomized(averagetumorvol~15-20mm3)toreceive5timesaweek,intraperitonealinjectionsofeitherDMSOorC188(50mg/kg)orC188-9(100mg/kg).Tumorvolumesaremeasuredtwiceweekly.Averagetumorvolumes6/πx(longdimension)x(shortdimension)2))arecalculatedandnormalizedtothevolumeatfirstdayoftreatmentandplottedcomparisonisdonebyttest(*p[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2022Nov4;13(1):6648.?JExpClinCancerRes.2020Nov23;39(1):252.?FrontImmunol.2021Feb26;12:584414.?FreeRadicBiolMed.8July2022.?MolOncol.2020Sep;14(9):2313-2331.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].SilvaKA,etal.InhibitionofStat3activationsuppressescaspase-3andtheubiquitin-proteasomesystem,leadingtopreservationofmusclemassincancercachexia.JBiolChem.2015Apr24;290(17):11177-87.[2].RedellMS,etal.Stat3signalinginacutemyeloidleukemia:ligand-dependentand-independentactivationandinductionofapoptosisbyanovelsmall-moleculeStat3inhibitor.Blood.2011May26;117(21):5701-9.[3].BharadwajU,etal.Small-moleculeinhibitionofSTAT3inradioresistantheadandnecksquamouscellcarcinoma.Oncotarget.2016May3;7(18):26307-30.[4].RedellMS,etal.Stat3signalinginacutemyeloidleukemia:ligand-dependentand-independentactivationandinductionofapoptosisbyanovelsmall-moleculeStat3inhibitor.Blood.2011;117(21):5701-5