Edicotinib-JNJ-40346527-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEdicotinibCat.No.:HY-109086CASNo.:1142363-52-7Synonyms:JNJ-40346527;JNJ-527分?式:C??H??N?O?分?量:461.6作?靶點(diǎn):c-Fms作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:16.67mg/mL(36.11mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1664mL10.8319mL21.6638mL5mM0.4333mL2.1664mL4.3328mL10mM0.2166mL1.0832mL2.1664mL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:≥1.67mg/mL(3.62mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(3.62mM);Clearsolution3.請(qǐng)依序添加每種溶劑：17%Polyethyleneglycol12-hydroxystearateinsalineSolubility:10mg/mL(21.66mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Edicotinib(JNJ-40346527)?種有效的、選擇性的、具有?腦通透性和?服活性CSF-1R抑制劑，IC50為3.2nM。Edicotinib對(duì)KIT和FLT3的抑制作?較?，IC50值分別為20nM和190nM。Edicotinib抑制?膠質(zhì)細(xì)胞的擴(kuò)張，減弱?膠質(zhì)細(xì)胞的增殖和神經(jīng)退?性變。Edicotinib可以?于阿爾茨海默病和類風(fēng)濕性關(guān)節(jié)炎的研究[1][2]。IC50&TargetIC50:3.2nM(CSF-1R)[1]20nM(KIT);190nM(FLT3)[2]體外研究Edicotinib(0.1nM-1μM;24hours)Leadstoadose-dependentdecreaseofCSF1RactivationandaconcurrentreductionofERK1andERK2phosphorylation.ThedoseresponsecurveshowstheeffectofJNJ-527onCSF1RandERK1/2,andtheIC50valuesare18.6nMand22.5nMforCSF1RandERK1/2,respectively[1].WesternBlotAnalysis[1]CellLine:N13microglialcellsConcentration:0.1nM,1nM,10nM,100nM,1000nMIncubationTime:24hoursResult:PreventedCSF1RandERK1/2phosphorylationinN13microglialcells體內(nèi)研究Edicotinib(oralgavage;3,10,30and100mg/kg;5days)significantlyinhibitsmicroglialproliferationinME7mice.Itdiminishesthenumberofmicroglia(totalCD45+CD11b+cells)onlyatthehighestdosetestedof100mg/kg,andJNJ-527depletesupto50%ofpatrollingbloodmonocytesateverydosetested(CD45+CD11bhighLy6Cintermediate/lowcells)withonlyatendencyforareductionintheproportionofinflammatorymonocytes(Ly6Chighcells)at100mg/kg[1].Edicotinibexhibitsagoodpharmacokinetic/pharmacodynamics(PK/PD)profile,themicroglialproliferationdatashowsanEC50of196/mland69ng/gcalculatedfromplasmaticandbraincompoundconcentration,respectively[1].Edicotinib(oralgavage;30mg/kg;33days)significantlyreducesthedensityofmicrogliainCA1ofthehippocampusofME7-prionmice(PU.1+cells)byupto30%.AndtheexpressionofIL-1βisalsoreduced,butnototherinflammatorycytokines[1].AnimalModel:C57BL/6J(Harlan)mice[1]Dosage:3,10,30and100mg/kg;5days2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:OralgavageResult:Didnotaffectmicroglialnumberswhenadministeredunder100mg/kg.AnimalModel:C57BL/6J(Harlan)mice[1]Dosage:30mg/kg;33daysAdministration:OralgavageResult:LimitedmicroglialexpansionandattenuatedbehaviouraldeficitsinME7-prionmice.REFERENCES[1].MancusoR,etal.CSF1RinhibitorJNJ-40346527attenuatesmicroglialproliferationandneurodegenerationinP301Smice.Brain.2019Oct1;142(10):3243-3264.[2].GenoveseMC,etal.ResultsfromaPhaseIIAParallelGroupStudyofJNJ-40346527,anOralCSF-1RInhibitor,inPatientswithActiveRheumatoidArthritisdespiteDisease-modifyingAntirheumaticDrugTherapy.JRheumatol.2015Oct;42(10):1752-60.McePdfHeightCaution