KRIBB11-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEKRIBB11Cat.No.:HY-100872CASNo.:342639-96-7分⼦式:C₁₃H₁₂N₆O₂分⼦量:284.27作⽤靶点:HSP;Apoptosis作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥27mg/mL(94.98mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.5178mL17.5889mL35.1778mL5mM0.7036mL3.5178mL7.0356mL10mM0.3518mL1.7589mL3.5178mL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。BIOLOGICALACTIVITY⽣物活性KRIBB11HSF1的抑制剂，IC50值为1.2μM。IC50&TargetHSF11/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.2μM(IC50)体外研究KRIBB11blockstheinductionofHSF1downstreamtargetproteinssuchasHSP27andHSP70.KRIBB11inducesgrowtharrestandapoptosisofHCT-116cells.KRIBB11inhibitsHSF1-dependentrecruitmentofp-TEFb(positivetranscriptionelongationfactorb)tothehsp70promoter[1].PARPandcaspase-3cleavageisincreasedincellstreatedwithKRIBB11.IncubatingRKOwithKRIBB11,showsatoxicthresholdofabout10µM,andanIC50of20-30µM[2].体内研究KRIBB11(50mg/kg,i.p.)resultsina47.4%inhibitionoftumorgrowthinnudemice,withoutbodyweightloss[1].PROTOCOLKinaseAssay[1]HCT-116cellsarewashedwithPBSandthenhomogenizedwitha27-gaugesyringeinbindingbuffer(10mmTris-HCl(pH7.4),50mmKCl,5mmMgCl2,1mmEDTA,and0.1mmNa3VO4).Thecelllysateiscentrifugedat13,000rpmfor30minat4°C,andthesupernatantiscollected.TheHCT-116celllysatesupernatantispreclearedbyincubatingwithDynabeadsM-280streptavidinfor30minat4°Candcapturedbymagnetseparation.Theclearedsupernatantsareincubatedwithbiotinyl-KRIBB11compound.Afterovernightincubationat4°C,proteinsassociatedwiththebiotinyl-KRIBB11compoundareprecipitatedwithDynabeadsM-280streptavidin.Precipitatedsamplesareseparatedbyamagnet.Samplesarewashedwith1mLofishingbuffercontaining50mmHEPES(pH7.5),50mmNaCl,1mmEDTA,1mmEGTA,0.1%Tween20,10%(v/v)glycerol,1mmNaF,0.1mmNa3VO4,andproteaseinhibitormixturetablets(1tablet/10mL).SamplesareboiledinSDSsamplebuffer,separatedby10%polyacrylamidegel,andimmunoblottedwithantibodiesagainstHSF1,HSF2,HSP90,orCDK9.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Cellsareseededonto96-wellplatesatadensityof6×103cellsperwellinMcCoy's5Amediumwith10%FBS.After24h,themediumisreplenwashedwithfreshcompletemediumcontainingchemicalsor0.1%DMSO.Afterincubationfor48h,thecellproliferationreagentWST-1isaddedtoeachwell.TheamountofWST-1formazanproducedismeasuredat450nmusinganELISAreader.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalSeven-week-oldfemaleinbredspecificpathogen-freeBalb/cnudemicearehousedundersterileconditionsAdministration[1]with12-hlight/darkcycles,andfedfoodandwateradlibitum.Fortheevaluationoftheinvivoanti-tumoractivityofKRIBB11,HCT-116cells(0.3mLof4×107cells/mL)areimplantedsubcutaneouslyintotherightflankofthemiceonday0.KRIBB11isdissolvedin10%dimethylacetamide,50%PEG300,and40%distilledwater.Whenthesizeoftumorsreached72.2mm3,thecompoundisadministeredintraperitoneallyatadoseof50mg/kg/dayfor18days.Tumorvolumesareestimatedbyusingtheformulalength(mm)×width(mm)×height(mm)/2.Todeterminethetoxicityofthecompound,thebodyweightoftumor-bearinganimalsisrecorded.Onday18,themicearesacrificed,andthetumorsareweighed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•SciTranslMed.2020May6;12(542):eaba0769.•EMBOMolMed.2021Jul5;e13792.•CancerRes.2019Oct15;79(20):5233-5244.•JExpClinCancerRes.2021Jan9;40(1):25.•CellDeathDis.2017Dec12;8(12):3203.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YoonYJ,etal.KRIBB11inhibitsHSP70synthesisthroughinhibitionofheatshockfactor1functionbyimpairingtherecruitmentofpositivetranscriptionelongationfactorbtothehsp70promoter.JBiolChem.2011Jan21;286(3):1737-47[2].SamarasingheB,etal.Heatshockfactor1confersresistancetoHsp90inhibitorsthroughp62/SQSTM1expressionandpromotionofautophagicflux.BiochemPharmac