KRIBB11-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEKRIBB11Cat.No.:HY-100872CASNo.:342639-96-7分?式:C??H??N?O?分?量:284.27作?靶點:HSP;Apoptosis作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥27mg/mL(94.98mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.5178mL17.5889mL35.1778mL5mM0.7036mL3.5178mL7.0356mL10mM0.3518mL1.7589mL3.5178mL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(fù)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?。BIOLOGICALACTIVITY?物活性KRIBB11HSF1的抑制劑，IC50值為1.2μM。IC50&TargetHSF11/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.2μM(IC50)體外研究KRIBB11blockstheinductionofHSF1downstreamtargetproteinssuchasHSP27andHSP70.KRIBB11inducesgrowtharrestandapoptosisofHCT-116cells.KRIBB11inhibitsHSF1-dependentrecruitmentofp-TEFb(positivetranscriptionelongationfactorb)tothehsp70promoter[1].PARPandcaspase-3cleavageisincreasedincellstreatedwithKRIBB11.IncubatingRKOwithKRIBB11,showsatoxicthresholdofabout10μM,andanIC50of20-30μM[2].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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