CCT251236-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECCT251236Cat.No.:HY-101026CASNo.:1693731-40-6分?式:C??H??N?O?分?量:552.62作?靶點:HSP作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥150mg/mL(271.43mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.8096mL9.0478mL18.0956mL5mM0.3619mL1.8096mL3.6191mL10mM0.1810mL0.9048mL1.8096mL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；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。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%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(4.52mM);ClearsolutionBIOLOGICALACTIVITY?物活性CCT251236通過熱休克轉(zhuǎn)錄因?1(hsf1)表型篩選得到的有?服活性的吡啶配體，抑制HSF1介導的HSP72誘導的IC50值為19nM。IC50&TargetHSP7219nM(IC50,SK-OV-3cells)體外研究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.體內(nèi)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?邊的抑制劑?師www.MedChemEAnimalModel:AthymicmicewithSK-OV-3cells[2]Dosage:20mg/kg;33daysAdministration:OraladminstationResult:WasefficaciousinSK-OV-3cellinduced-tumormicemodel.戶使?本產(chǎn)品發(fā)表的科研?獻?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