Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEKNK437Cat.No.:HY-100110CASNo.:218924-25-5Synonyms:HeatShockProteinInhibitorI分?式:C??H??NO?分?量:245.23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:31.25mg/mL(127.43mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.0778mL20.3890mL40.7780mL5mM0.8156mL4.0778mL8.1556mL10mM0.4078mL2.0389mL4.0778mL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:1.67mg/mL(6.81mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性KNK437HSP抑制劑，能夠抑制HSP105，HSP70和HSP40的活化。IC50&TargetHSP105HSP70HSP40體外研究KNK437inhibitstheactivationofseveralHSPsincludingHSP105,HSP70,andHSP40inCOLO320DM(humancoloncarcinoma)cells.KNK437(100μM)inhibitsthermotoleranceinCOLO320DMcellsafterthefirstheattreatment.KNK437showsinhibitoryeffectsonthermotolerancedose-dependentlyinCOLO320DMcells(0-200μM)andHeLaS3cells(100,200μM)[1].KNK437(100μM)exhibitsinhibitoryactivitiesagainstthemethylationofH3-Lys4beforeorafterheat-treatmentinHSC4cellsandKBcells,butdoesnotaffectthatofH3Lys9.KNK437alsosuppressestheexpressionofHSP70[3].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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