C188-9-TTI-101-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEC188-9Cat.No.:HY-112288CASNo.:432001-19-9Synonyms:TTI-101分⼦式:C₂₇H₂₁NO₅S分⼦量:471.52作⽤靶点:STAT;Apoptosis作⽤通路:JAK/STATSignaling;StemCell/Wnt;Apoptosis储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:25mg/mL(53.02mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1208mL10.6040mL21.2080mL5mM0.4242mL2.1208mL4.2416mL10mM0.2121mL1.0604mL2.1208mL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(protectfromlight)。-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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.41mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性C188-9(TTI-101)Stat3的抑制剂，其Kd值为4.7nM。C188-9抑制G-CSF诱导的STAT3激活和STAT3依赖性因表达。C188-9诱导AML细胞系和原代标本凋亡，抑制原代AML细胞集落形成。IC50&TargetSTAT34.7nM(Kd)体外研究C188-9isaStat3inhibitor,withaKdof4.7nM[1].TheIC50sofC188-9toinhibitStat3activationinAMLcelllinesareintherangeof4-7μM,andinprimaryAMLsamplestheIC50sareintherangeof8-18μM.Forapoptosisstudies,AMLcelllinesandprimarysamplesaretreatedfor24hourswithC188-9,thenapoptoticcellsarequantifiedbyFACSanalysisforannexinV-labeledcells.TheEC50sforapoptosisinductionarequitevariable,rangingfrom6μMtoover50μM[2].体内研究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.户使⽤本产品发表的科研⽂献•NatCommun.2022Nov4;13(1):6648.•JExpClinCancerRes.2020Nov23;39(1):252.•FrontImmunol.2021Feb26;12:584414.•FreeRadicBiolMed.8July2022.•MolOncol.2020Sep;14(9):2313-2331.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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