Delgocitinib-JTE-052-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDelgocitinibCat.No.:HY-109053CASNo.:1263774-59-9Synonyms:JTE-052分⼦式:C₁₆H₁₈N₆O分⼦量:310.35作⽤靶点:JAK作⽤通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥58mg/mL(186.89mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.2222mL16.1108mL32.2217mL5mM0.6444mL3.2222mL6.4443mL10mM0.3222mL1.6111mL3.2222mL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1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE、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：1%DMSO>>99%salineSolubility:≥0.5mg/mL(1.61mM);Clearsolution2.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(8.06mM);Clearsolution3.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.06mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Delgocitinib(JTE-052)⼀种特异性的JAK抑制剂，对JAK1,JAK2,JAK3和Tyk2的IC50值分别为2.8，2.6，13和58nM[1]。IC50&TargetJAK1JAK2JAK3Tyk22.8nM(IC50)2.6nM(IC50)13nM(IC50)58nM(IC50)体外研究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].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•JClinMed.2020Mar24;9(3):891.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TanimotoA,etal.PharmacologicalpropertiesofJTE-052:anovelpotentJAKinhibitorthatsuppressesvariousinflammatoryresponsesinvitroandinviv