Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEFedratinibhydrochloridehydrateCat.No.:HY-10409ACASNo.:1374744-69-0Synonyms:TG-101348hydrochloridehydrate;SAR302503hydrochloridehydrate分?式:C??H??Cl?N?O?S分?量:615.62作?靶點(diǎn):JAK;Apoptosis作?通路:Epigenetics;JAK/STATSignaling;StemCell/Wnt;Apoptosis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:250mg/mL(406.09mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.6244mL8.1219mL16.2438mL5mM0.3249mL1.6244mL3.2488mL10mM0.1624mL0.8122mL1.6244mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。BIOLOGICALACTIVITY?物活性Fedratinibhydrochloridehydrate(TG-101348hydrochloridehydrate)?種有效的，選擇性的，ATP競(jìng)爭(zhēng)性和具有?服活性的JAK2抑制劑，對(duì)于JAK2和JAK2V617F激酶的IC50均為3nM。Fedratinibhydrochloridehydrate對(duì)JAK2的選擇性分別?JAK1和JAK3?35倍和334倍。Fedratinibhydrochloridehydrate可誘導(dǎo)癌細(xì)胞凋亡(apoptosis)，并可?于?髓增?性疾病的研究。1/2MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEIC50&TargetJAK2JAK2(V617F)Flt3Ret3nM(IC50)3nM(IC50)15nM(IC50)48nM(IC50)體外研究Fedratinib(TG101348)inhibitsproliferationofahumanerythroblastleukemia(HEL)celllinethatharborstheJAK2V617Fmutation,aswellasamurinepro-BcelllineexpressinghumanJAK2V617F(Ba/F3JAK2V617F),withanIC50valueofapproximately300nMforeitherline.ProliferationofparentalBa/F3cellswasinhibitedtoacomparablelevel,withanIC50valueof-420nM[1].ExposureofthesecellstoFedratinib(TG101348)(0.1μM,0.3μM,1μM,3μM,and10μM)reducesSTAT5phosphorylationatconcentrationsthatparalleltheconcentrationsrequiredtoinhibitcellproliferation[1].Fedratinib(TG101348)(0.1μM,0.3μM,1μM,3μM,and10μM)inducesapoptosisinbothHELandBa/F3JAK2V617Fcellsinadose-dependentmanner[1].體內(nèi)研究Fedratinib(TG101348;60-120mg/kg;oralgavage;twicedaily;for42days;C57Bl/6mice)trewatmentshowsadose-dependentreductioninpolycythemiaandamarkeddose-dependentreductioninsplenomegalyoftreatedanimals[1].AnimalModel:C57Bl/6miceinducedbytheJAK2V617Fmutation[1]Dosage:60mg/kg,120mg/kgAdministration:Oralgavage;twicedaily;for42daysResult:Showedastatisticallysignificantreductioninhematocritandleukocytecount,adose-dependentreduction/eliminationofextramedullaryhematopoiesis.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?CellSyst.2018Apr25;6(4):424-443.e7.?EMBORep.2019Jun;20(6):e47202.?MolTherNucleicAcids.2020Sep4;21:900-915.?AmJClinNutr.2020Jan1;111(1):110-121.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WernigG,etal.EfficacyofTG101348,aselectiveJAK2inhibitor,intreatmentofamurinemodelofJAK2V617F-inducedpolycythemiavera.CancerCell.2008Apr;13(4):311-20.[2].GeronI,etal.SelectiveinhibitionofJAK2-drivenerythroiddifferentiationofpolycythemiaveraprogenitors.CancerCell.2008Apr;13(4):321-30.McePdfHeightCaution:Producthasnotbeenfullyvalidated