KNK437-Heat-Shock-Protein-Inhibitor-I-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEKNK437Cat.No.:HY-100110CASNo.:218924-25-5Synonyms:HeatShockProteinInhibitorI分⼦式:C₁₃H₁₁NO₄分⼦量:245.23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:31.25mg/mL(127.43mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.0778mL20.3890mL40.7780mL5mM0.8156mL4.0778mL8.1556mL10mM0.4078mL2.0389mL4.0778mL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:1.67mg/mL(6.81mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性KNK437HSP抑制剂，能够抑制HSP105，HSP70和HSP40的活化。IC50&TargetHSP105HSP70HSP40体外研究KNK437inhibitstheactivationofseveralHSPsincludingHSP105,HSP70,andHSP40inCOLO320DM(humancoloncarcinoma)cells.KNK437(100μM)inhibitsthermotoleranceinCOLO320DMcellsafterthefirstheattreatment.KNK437showsinhibitoryeffectsonthermotolerancedose-dependentlyinCOLO320DMcells(0-200μM)andHeLaS3cells(100,200μM)[1].KNK437(100μM)exhibitsinhibitoryactivitiesagainstthemethylationofH3-Lys4beforeorafterheat-treatmentinHSC4cellsandKBcells,butdoesnotaffectthatofH3Lys9.KNK437alsosuppressestheexpressionofHSP70[3].体内研究KNK437isaweaklytoxicagent.KNK437(62.5-400mg/kg)recoversbodyweightlossesoftumor-freeCD-1(ICR)mice.KNK437(200mg/kg)aloneshowsnoantitumoreffectsanddoesnotincreasethethermosensitivityofnontoleranttumors.KNK437improvestheantitumoreffectsoffractionatedheattreatmentat44°Cat200mg/kginasynergisticmanner.KNK437(200mg/kg,i.p.)suppressestheinductionofthermotolerancewhenadministrated6hbeforetheinitialheating[2].PROTOCOLCellAssay[1]Heattreatmentsat42°Cfor90minareperformedinaCO2incubatorusing25-cm2plasticflasks.Cells(1×105)areseededintheflasks,incubatedat37°Cfor48h,andthenheatedbyimmersingtheflasksinawaterbath(45°C±0.05°C).KNK437andquercetinaredissolvedinDMSObeforebeingaddedattheindicatedconcentrations.ThefinalconcentrationofDMSOineachculturemediumis0.25%(v/v),irrespectiveoftheconcentrationsofthedrugs.ThesameconcentrationofDMSOisusedasacontrol.SodiumarseniteisdissolvedinPBSataconcentrationof80mMandaddedtothemedium.Cellsaretreatedwith300μMsodiumarseniteat37°Cfor1.5h,rinsed,andthenincubatedat37°Cfor5hbefore45°Cheatchallenge[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalTosubjectthetumorstohyperthermia,therightfootofeachmouseisimmersedinawaterbathmaintainedAdministration[2]atthedesiredtemperaturetoanaccuracyof±0.05°C.Afterthemousehasbeenanesthetizedwith50mg/kgpentobarbitalsodiumsolution,thetumor-bearinglegispulleddownintothewaterbathusingaspecialsinker(weighing-45g)tapedtotheskinofthetoe.Careistakennottoimpairthebloodflowinthelimb.Whiletheextendedrightlegisreceivinglocalheat,themouseisair-cooled.KNK437isdissolvedinoliveoilimmediatelybeforeuse.TheKNK437isadministeredi.p.6hbeforethefirstheattreatment.Itisusedmainlyataconcentrationof200mg/kg[2].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•FishShellfishImmunol.2017Nov;70:185-194.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YokotaS,etal.Benzylidenelactamcompound,KNK437,anovelinhibitorofacquisitionofthermotoleranceandheatshockproteininductioninhumancoloncarcinomacells.CancerRes.2000Jun1;60(11):2942-8.[2].KoishiM,etal.TheeffectsofKNK437,anovelinhibitorofheatshockproteinsynthesis,ontheacquisitionofthermotoleranceinamurinetransplantabletumorinvivo.ClinCancerRes.2001Jan;7(1):215-9.[3].MatsudaK,etal.EffectsofKNK437onheat-inducedmethylationofhistoneH3inhumanoralsquamouscellcarcinomacells.IntJHyperthermia.2