CA-074-methyl-ester-CA-074Me-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECA-074methylesterCat.No.:HY-100350CASNo.:147859-80-1Synonyms:CA-074Me分?式:C??H??N?O?分?量:397.47作?靶點(diǎn):Cathepsin作?通路:MetabolicEnzyme/Protease儲(chǔ)存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(251.59mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5159mL12.5796mL25.1591mL5mM0.5032mL2.5159mL5.0318mL10mM0.2516mL1.2580mL2.5159mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(qǐng)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(6.29mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.29mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.29mM);ClearsolutionBIOLOGICALACTIVITY?物活性CA-074methylester?種特異性的CathepsinB抑制劑，具有保護(hù)神經(jīng)，抗癌、抗炎等多種?物活性。體外研究CA-074Me(5μMand50μM)inhibitsRANKL-inducedosteoclastogenesisinBMMcellsderivedfromC57BL/6JandNOD/ShiLtJmice.CA-074Meexertsitsanti-osteoclastogeniceffectwithin24hourspost-RANKLstimulationinvitro.CA-074Medoesnotexertitsanti-osteoclastogeniceffectviatheMAPK-ERKsignalingcascade.CA-074Meinhibitsc-FOSupregulationandsubsequentNFATc1autoamplificationfollowingRANKLstimulation.[2].CA-074MereducesapoptosisinducedbyCVB1[3].體內(nèi)研究HippocampalCA1neuronalprogrammednecrosisinducedbyglobalcerebralI/RinjuryispreventedbyCA074-me(1μg,10μg)bothpre-treatmentandpost-treatment.Theruptureoflysosomalmembraneandtheleakageofcathepsin-B,andthisisstronglyinhibitedbyCA074-mepre-treatment.TheoverexpressionandnucleartranslocationofRIP3andthereductionofNAD+levelafterI/Rinjuryarealsoinhibited,whiletheupregulationofHsp70isstrengthenedbyCA074-mepre-treatment[1].CA-074Me(30mg/kg)iscapableofinhibitingosteoclastogenesisandbonedegradationinvivo[2].IntheCVB+CA-074Me(4mg/kg/dayi.m.)guineapigsgroup,thescoresofinflammationsignificantlydecreaseincomparisonwiththeCVB+Nonegroup.InCVB+CA-074Megroup,thenumberofCD8+Tcellsdecreaseincomparisonwiththeshamgroup[3].PROTOCOLKinaseAssay[2]Aftersevendaysofcellcultureandosteoclastgeneration,themediaisremovedandwashedthreetimeswithPBS.BMMsarefixedwithafixingsolutionsuppliedbythemanufacturer.Thecellsareincubatedat37°Cwithasolutioncontainingdeionizedwater,FastGarnetGBC,Naptholphosphate,Acetate,andTartratefor1h.Thestainingsolutionisremoved,washedwithPBS(3×),andair-dried.TRAPpositivecellswiththreeormorenucleiacrosswholecultureareaarecountedasmultinucleatedosteoclastsusinglightmicroscopy.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRANKL(0.08mg/kg)withandwithoutCA-074Me(10mg/kgor30mg/kg)aremixedinsterile,Administration[2]nonimmunogenic1%Extracel-HPgel.Thegeliscomposedofthiol-modifiedsodiumhyaluronate,thiol-modifiedheparin,thiol-modifiedgelatin,anddegasseddeionizedsterilewater.Thehydrogelmixtureispreparedinanaseptichoodusingasterilesyringe.ThecontrolshamhydrogelcontainedsterilePhosphateBufferedSaline(PBS)withoutanycytokines.Theosteolysisgroupisgiven0.08mg/kgRANKLinahydrogeltoinducepathologicboneloss.Thehydrogel-only,hydrogel-RANKL,andhydrogel-RANKL-CA-074Memixtureisinjectedinto8-weekoldmalemicecalvariuminanaseptichood(n=5)followinggeneral2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEanesthesia(80mg/kgofketamineand7mg/kgofxylazine).Afterfourdays,thecalvariaareexcised,fixedin4%formaldehydefor24h,decalcifiedin20%EDTAforoneweek,andsectionedintoslidesfromparaffinblocks.TheslidesundergoTartrate-ResistantAcidPhosphatase(TRAP)stainingtoidentifyosteoclasts.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellMolImmunol.2020Mar;17(3):283-299.?EmergMicrobesInfect.2022Dec;11(1):483-497.?SciAdv.2022Nov11;8(45):eabn9912.?JHazardMater.2022May10;436:129093.?Theranostics.2021Oct11;11(20):9821-9832.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XuY,etal.ProtectivemechanismsofCA074-me(otherthancathepsin-Binhibition)againstprogrammednecrosisinducedbyglobalcerebralischemia/reperfusioninjuryinrats.BrainResBull.2016Jan;120:97-105[2].PatelN,etal.CA-074MecompoundinhibitsosteoclastogenesisviasuppressionoftheNFATc1andc-FOSsignalingpathways.JOrthopRes.2015Oct;33(10):1474-86[3].ZhangL,etal.TreatmentwithCA-074Me,aCathepsinBinhibitor,reduceslunginterstitialinflammationandfibrosisinara