Fenebrutinib-GDC-0853-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFenebrutinibCat.No.:HY-19834CASNo.:1434048-34-6Synonyms:GDC-0853分?式:C??H??N?O?分?量:664.8作?靶點:Btk作?通路:ProteinTyrosineKinase/RTK儲存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實驗DMSO:≥23mg/mL(34.60mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.5042mL7.5211mL15.0421mL5mM0.3008mL1.5042mL3.0084mL10mM0.1504mL0.7521mL1.5042mL請根據(jù)產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥1mg/mL(1.50mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(1.50mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1mg/mL(1.50mM);ClearsolutionBIOLOGICALACTIVITY?物活性Fenebrutinib(GDC-0853)?種有效的，具有?服活性的，選擇性和?共價的布魯頓酪氨酸激酶(Btk)抑制劑，對野?型Btk，及突變型C481S，C481R，T474I，T474M的Ki分別為0.91nM，1.6，1.3，12.6和3.4nM。有潛??于類風濕關節(jié)炎和系統(tǒng)性紅斑狼瘡的研究[1][2]。IC50&TargetKi:0.91nM(BtkWT),1.6nM(BtkC481S),1.3nM(BtkC481R),12.6nM(BtkT474I),and3.4nM(BtkT474M)[1]體外研究Fenebrutinib(GDC-0853)inhibitsCD69expressiononCD19+BcellsinhumanwholebloodwithanIC50of8.4±5.6nM.FenebrutinibinhibitsCD63expressiononbasophilswithanIC50of30.7±4.1nM[2].Fenebrutinibsuppressesanti-IgMinducedBtkY223autophosphorylationinhumanwholeblood(IC50=11nM)[2].體內研究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.戶使?本產品發(fā)表的科研?獻?Leukemia.2021Feb1.?JCIInsight.2019Jun20;4(12).pii:127566.?IntJMolSci.2022,23(1),76.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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