Ilginatinib-hydrochloride-NS-018-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIlginatinibhydrochlorideCat.No.:HY-19631BCASNo.:1239358-85-0Synonyms:NS-018hydrochloride分?式:C??H??ClFN?分?量:425.89作?靶點(diǎn):JAK作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥35mg/mL(82.18mM)H2O:2mg/mL(4.70mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3480mL11.7401mL23.4802mL5mM0.4696mL2.3480mL4.6960mL10mM0.2348mL1.1740mL2.3480mL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(sealedstorage,awayfrommoisture)。-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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.87mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ilginatinibhydrochloride(NS-018hydrochloride)?種?度有效的，可?服的JAK2抑制劑，IC50值為0.72nM，對(duì)其選擇性對(duì)JAK1的46倍(IC50,33nM)，JAK3的54倍(IC50,39nM)，以及Tyk2的22倍(IC50,22nM)。IC50&TargetJAK2Tyk2JAK1JAK30.72nM(IC50)22nM(IC50)33nM(IC50)39nM(IC50)體外研究Ilginatinibhydrochloride(NS-018hydrochloride)isahighlyactiveJAK2inhibitor,withanIC50of0.72nM,46-,54-,and31-foldselectivityforJAK2overJAK1(IC50,33nM),JAK3(IC50,39nM),andTyk2(IC50,22nM).IlginatinibhydrochloridealsoinhibitsSrc-familykinases,especiallySRCandFYN,andweaklyinhibitsABLandFLT3with45-and90-foldselectivityforJAK2,respectively.IlginatinibhydrochlorideshowspotentinhibitoryactivityagainstcelllinesJAK2V617ForMPLW515LmutationsortheTEL-JAK2fusiongene(expressingaconstitutivelyactivatedJAK2)withIC50of11-120?nM,buthasonlyminimalcytotoxicityagainstmostotherhematopoieticcelllinesthathavenoconstitutivelyactivatedJAK2[1].Ilginatinibhydrochloride(0.5μM)preferentiallysuppressescolony-formingunitgranulocyte/macrophage(CFU-GM)formationfrommyelodysplasticsyndrome(MDS)-derivedbonemarrowmononuclearcells(BMMNCs).Ilginatinibhydrochloride(1μM)suppressesthephosphorylationofSTAT3(thedownstreamkinaseofJAK2)inCFU-GM-formingcellsfromMDSpatients[2].體內(nèi)研究Ilginatinibhydrochloride(NS-018hydrochloride)(12.5,25,50,100mg/kg,p.o.)potentlyprolongsthesurvivalofmiceandreducessplenomegalyinamouseBa/F3-JAK2V617Fdiseasemodel[1].Ilginatinibhydrochloride(25,50mg/kg,p.o.)significantlyreducesleukocytosis,hepatosplenomegalyandextramedullaryhematopoiesis,improvesnutritionalstatus,andprolongssurvivalinJAK2V617Ftransgenicmice[1].PROTOCOLCellAssay[2]Bonemarrowmononuclearcells(BMMNCs)fromhealthyvolunteersandmyelodysplasticsyndrome(MDS)patientsareincubatedinMethoCultGFH4434methylcellulosemediumcontainingvarioushematopoieticcytokinesat1.0×105cells/mLwithorwithoutIlginatinib(NS-018)at37°Cinahumidifiedatmosphereof5%CO2.CommerciallyavailablepurifiednormalhumanCD34-positive(CD34+)BMcellsareusedasacontrol.Burst-formingunit-erythroid(BFU-E)andcolonyformingunit-granulocyte/macrophage(CFU-GM)coloniesarecountedunderaninvertedmicroscopeonday14ofculture[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]FemaleBALB/cnudemiceareplacedinblanketcagesinanenvironmentmaintainedat21-25°Cand45-2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE65%relativehumidity,withartificialilluminationfor12?handaventilationfrequencyofatleast15?times/h.Theyareallowedfreeaccesstofoodpelletsandtapwater.Ba/F3-JAK2V617Fcells(106permouse)areinoculatedintravenouslyinto7-week-oldmice.Administrationofvehicle(0.5%methylcellulose)orIlginatinib(NS-018)twicedailybyoralgavagebeginsthedayaftercellinoculation.Survivalismonitoreddaily,andmoribundmicearehumanelykilledandtheirtimeofdeathisrecordedforpurposesofsurvivalanalysis.Inaparallelstudy,allmicearehumanelykilledafter8daysofadministration,andtheirspleensareremovedandweighed[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].NakayaY,etal.EfficacyofNS-018,apotentandselectiveJAK2/Srcinhibitor,inprimarycellsandmousemodelsofmyeloproliferativeneoplasms.BloodCancerJ.2011Jul;1(7):e29.[2].KurodaJ,etal.NS-018,aselectiveJAK2inhibitor,preferentiallyinhibitsCFU-GMcolonyformationbybonemarrowmononuclearcellsfromhigh-riskmyelodysplasticsyndrome