Fedratinib-TG-101348-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFedratinibCat.No.:HY-10409CASNo.:936091-26-8Synonyms:TG-101348;SAR302503分?式:C??H??N?O?S分?量:524.68作?靶點:JAK;Apoptosis作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(238.24mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9059mL9.5296mL19.0592mL5mM0.3812mL1.9059mL3.8118mL10mM0.1906mL0.9530mL1.9059mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.96mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.96mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.96mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.87mg/mL(5.47mM);Clearsolution5.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:2.87mg/mL(5.47mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Fedratinib(TG-101348)?種有效的，選擇性的，ATP競爭性和具有?服活性的JAK2抑制劑，對于JAK2和JAK2V617F激酶的IC50均為3nM。Fedratinib對JAK2的選擇性分別?JAK1和JAK3?35倍和334倍。Fedratinib可誘導(dǎo)癌細胞凋亡(apoptosis)，并可?于?髓增?性疾病的研究。IC50&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.戶使?本產(chǎn)品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?MolCancer.2021May29;20(1):80.?SignalTransductTargetTher.2022Feb23;7(1):52.?SignalTransductTargetTher.2020Dec26;5(1):295.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?CellSyst.2018Apr25;6(4):424-443.e7.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: