Fenebrutinib-GDC-0853-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEFenebrutinibCat.No.:HY-19834CASNo.:1434048-34-6Synonyms:GDC-0853分⼦式:C₃₇H₄₄N₈O₄分⼦量:664.8作⽤靶点:Btk作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性数据体外实验DMSO:≥23mg/mL(34.60mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.5042mL7.5211mL15.0421mL5mM0.3008mL1.5042mL3.0084mL10mM0.1504mL0.7521mL1.5042mL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(storedundernitrogen)。-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、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：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥1mg/mL(1.50mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(1.50mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1mg/mL(1.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Fenebrutinib(GDC-0853)⼀种有效的，具有⼝服活性的，选择性和⾮共价的布鲁顿酪氨酸激酶(Btk)抑制剂，对野⽣型Btk，及突变型C481S，C481R，T474I，T474M的Ki分别为0.91nM，1.6，1.3，12.6和3.4nM。有潜⼒⽤于类风湿关节炎和系统性红斑狼疮的研究[1][2]。IC50&TargetKi:0.91nM(BtkWT),1.6nM(BtkC481S),1.3nM(BtkC481R),12.6nM(BtkT474I),and3.4nM(BtkT474M)[1]体外研究Fenebrutinib(GDC-0853)inhibitsCD69expressiononCD19+BcellsinhumanwholebloodwithanIC50of8.4±5.6nM.FenebrutinibinhibitsCD63expressiononbasophilswithanIC50of30.7±4.1nM[2].Fenebrutinibsuppressesanti-IgMinducedBtkY223autophosphorylationinhumanwholeblood(IC50=11nM)[2].体内研究Fenebrutinib(GDC-0853)dose-dependentlyreducesanklethicknessfollowingonce(0.06,0.25,1,4,and16mg/kgQD;orally)ortwice(0.125,0.5,and2mg/kgBID;orally)dailyinfemaleLewisratswithdevelopingcollagen-inducedarthritis[2].Fenebrutinib(0.2mg/kgIVand1.0mg/kgPO;forrats)and(0.2mg/kgIVand0.5mg/kgPOfordogs)demonstratesthehalf-lives(t1/2s)of2.2and3.8hInrats,anddogs,respectively[2].AnimalModel:FemaleLewisratswithdevelopingcollagen-inducedarthritis(CIA)[2]Dosage:0.06,0.25,1,4,and16mg/kgoncedaily(QD);0.125,0.5,and2mg/kgtwicedaily(BID)Administration:Dosedorally;for16daysResult:Dose-dependentlyreducedanklethicknessfollowingQDandBIDdosingregimens.户使⽤本产品发表的科研⽂献•Leukemia.2021Feb1.•JCIInsight.2019Jun20;4(12).pii:127566.•IntJMolSci.2022,23(1),76.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].EricksonRI,etal.Bruton'sTyrosineKinaseSmallMoleculeInhibitorsInduceaDistinctPancreaticToxicityinRats.JPharmacolExpTher.2017Jan;360(1):226-238.[2].CrawfordJJ,etal.DiscoveryofGDC-0853:APotent,Selective,andNoncovalentBruton'sTyrosineKinaseInhibitorinEarlyClinicalDevelopment.JMedChem.2018Mar22;61(6):2227-2245.McePdfHeightCaution:Producthasnotbeenfullyv