CCT251236-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECCT251236Cat.No.:HY-101026CASNo.:1693731-40-6分⼦式:C₃₂H₃₂N₄O₅分⼦量:552.62作⽤靶点:HSP作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥150mg/mL(271.43mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8096mL9.0478mL18.0956mL5mM0.3619mL1.8096mL3.6191mL10mM0.1810mL0.9048mL1.8096mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(4.52mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CCT251236通过热休克转录因⼦1(hsf1)表型筛选得到的有⼝服活性的吡啶配体，抑制HSF1介导的HSP72诱导的IC50值为19nM。IC50&TargetHSP7219nM(IC50,SK-OV-3cells)体外研究CCT251236(0-100nM;24hours)displaysadesiredbalanceofinvitroproperties,whilemaintainingexcellentcellularactivitywithapIC50=7.73±0.07(IC50=19nM)forinhibitionofHSF1-mediatedHSP72induction.ThefreeGI50is1.1nMinSK-OV-3cellsthatcalculatedfromthefreefractioninthecellassay[1].CCT251236(0-100nM;24hours)blocks17-AAGinducedheHSF1-mediatedheat-shockproteins,HSP72andHSP27expressionasaconcentrationmannerinSK-OV-3cells[1].CCT251236(0-100nM;24hours),pre-treatedwith250nM17-AAGfor6h,blockstheinductionofHSPA1AmRNAby17-AAGinadosedependentmanner[1].WesternBlotAnalysis[1]CellLine:SK-OV-3cellsConcentration:0nM;10nM;100nMIncubationTime:24hoursResult:InhibitedHSP72andHSP27expressionatthedoseof10nM.RT-PCR[1]CellLine:SK-OV-3cellsConcentration:0nM;10nM;100nMand1000nMIncubationTime:24hoursResult:DecreasedHSPA1AmRNAlevel.体内研究CCT251236(oraladminstation;5or20mg/kg)innontumorbearingimmunocompetentBALB/cmiceexhibitsfreeCav0-24hvalueof2.0nMand1.2nM,respectively[2].CCT251236(oraladminstation;20mg/kg;33days)hasacleartherapeuticefficacyinmicewithatumorgrowthinhibition(%TGI)of70%basedonfinaltumorvolumes.After33days,themeantumorweightsdecreases64%whencomparestocontrolgroup.Inaddition,thecompound’sbasicityandhighvolumeofdistributionshowsintumorwithtumorconcentrationsofCCT251236ashighas940nM[2].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:AthymicmicewithSK-OV-3cells[2]Dosage:20mg/kg;33daysAdministration:OraladminstationResult:WasefficaciousinSK-OV-3cellinduced-tumormicemodel.户使⽤本产品发表的科研⽂献•ProcNatlAcadSciUSA.2021Feb16;118(7):e2014457118.•MolOncol.2019Feb;13(2):322-337.•MolMed.2021May30;27(1):53.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CheesemanMD,etal.DiscoveryofaChemicalProbeBisamide(CCT251236):AnOrallyBioavailableEfficaciousPirinLigandfromaHeatShockTranscriptionFactor1(HSF1)PhenotypicScreen.JMedChem.2017Jan12;60(1):180-201.McePdfHeightCaution:Producthasnotbeenfu