Delgocitinib-JTE-052-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDelgocitinibCat.No.:HY-109053CASNo.:1263774-59-9Synonyms:JTE-052分?式:C??H??N?O分?量:310.35作?靶點(diǎn):JAK作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt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:≥58mg/mL(186.89mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2222mL16.1108mL32.2217mL5mM0.6444mL3.2222mL6.4443mL10mM0.3222mL1.6111mL3.2222mL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1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE、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：1%DMSO>>99%salineSolubility:≥0.5mg/mL(1.61mM);Clearsolution2.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(8.06mM);Clearsolution3.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.06mM);ClearsolutionBIOLOGICALACTIVITY?物活性Delgocitinib(JTE-052)?種特異性的JAK抑制劑，對(duì)JAK1,JAK2,JAK3和Tyk2的IC50值分別為2.8，2.6，13和58nM[1]。IC50&TargetJAK1JAK2JAK3Tyk22.8nM(IC50)2.6nM(IC50)13nM(IC50)58nM(IC50)體外研究Intheenzymaticassays,DelgocitinibpotentlyinhibitsalloftheJAKsubtypeswithIC50valuesof2.8±0.6,2.6±0.2,13±0and58±9nMforJAK1,JAK2,JAK3andTyk2,respectively.Lineweaver-BurkplotsshowthattheinhibitionmodeofDelgocitinibtowardallJAKsiscompetitivewithATPwithKivaluesof2.1±0.3,1.7±0.0,5.5±0.3and14±1nMforJAK1,JAK2,JAK3andTyk2,respectively.Inthesecell-basedcytokinesignalingassays,DelgocitinibinhibitsthephosphorylationofStatproteinsinducedbyIL-2,IL-6,IL-23,GM-CSF,andIFN-αwithIC50valuesof40±9,33±14,84±11,304±22and18±3nM,respectively.DelgocitinibalsoinhibitsIL-2-inducedproliferationofTcellsinaconcentration-dependentmanner(IC50=8.9±3.6nM),anditspotencyissimilartothatofCP-690550(IC50=16nM)[1].體內(nèi)研究DelgocitinibdecreasestheIFN-γproduction,butthepotencyofthe1-hprioradministrationishigherthanthatofthe6-hprioradministration(ED50=0.24versus1.3mg/kg).Intheadministrationfromday1,Delgocitinibpreventsthedevelopmentofhindpawswellingandhistologicalchangesofinflammatorycellinfiltrationandsynovialcellhyperplasia.Delgocitinibinhibitsradiographicandhistologicalchangesofbonedestructionandcartilagedestruction.Intheadministrationfromday15,Delgocitinibdecreasesthepawswellinginadose-dependentmanner.Inaddition,Delgocitinibamelioratestheinflammatorycellinfiltration,synovialcellhyperplasia,andcartilage/bonedestructionsinthehistologicalandradiographicexaminationsattheendofthestudy[1].PROTOCOLCellAssay[1]FordeterminationofIL-2-inducedTcellproliferation,humanTcellsarepreculturedwith10μg/mLPHA-Mfor3daysandplatedin96-wellplatesat1.0×104cells/wellinthepresenceorabsenceofvariousconcentrationsofDelgocitinib.FollowingpreincubationwithDelgocitinibfor30minat37°C,thecellsarestimulatedbyadding20ng/mLrecombinanthumanIL-2toeachwellandincubatedfor3daysat37°Cunder5%CO2.Aftercompletionofthecultureperiod,thecellsareharvestedwitha96-wellharvesterandcountedinascintillationcounter[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalLewisratsareusedinthisstudy.First,collagen-inducedarthritis(CIA)isinducedinrats.LewisratsareAdministration[1]immunizedwith1mLoftheemulsion(1mgoftypeIIcollagen)viatenintradermalinjectionsonthebackunderanesthesia.Theratsarethenchallengedwith0.2mLoftheemulsioninjectedintothebaseofthetailonday8underanesthesia.Delgocitinibisgivenorallyoncedailyfromday1today21(preventiveadministration)orfromday15today28(therapeuticadministration).Afterarthritisinduction,thehindpawvolumeismeasuredbyawaterdisplacementmethodusingaplethysmometer.Onday22orday29,theratsareeuthanized,andtheirhindpawsareexcisedandX-rayedorprocessedforhistologicalevaluation[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JClinMed.2020Mar24;9(3):891.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TanimotoA,etal.PharmacologicalpropertiesofJTE-052:anovelpotentJAKinhibitorthatsuppressesvariousinflammatoryresponsesinvitroandinviv