Olverembatinib-dimesylate-GZD824-dimesylate-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOlverembatinibdimesylateCat.No.:HY-15666ACASNo.:1421783-64-3Synonyms:GZD824dimesylate;HQP1351dimesylate分?式:C??H??F?N?O?S?分?量:724.77作?靶點:Bcr-Abl作?通路:ProteinTyrosineKinase/RTK儲存?式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(172.47mM;Needultrasonic)H2O:≥50mg/mL(68.99mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.3797mL6.8987mL13.7975mL5mM0.2759mL1.3797mL2.7595mL10mM0.1380mL0.6899mL1.3797mL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(sealedstorage,awayfrommoistureandlight)。-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(2.87mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.87mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.87mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)lverembatinib(GZD824)dimesylate?種?效的，具有?服活性的pan-Bcr-Abl抑制劑。Olverembatinibdimesylate能?泛?有效地抑制突變型Bcr-Abl。Olverembatinibdimesylate對天然的Bcr-Abl和Bcr-AblT315I作?的IC50值分別為0.34nM和0.68nM。Olverembatinibdimesylate具有抗腫瘤作?[1]。IC50&TargetIC50:0.68nM(Bcr-AblT315I),0.27nM(Bcr-AblE255K),0.71nM(Bcr-AblG250E),0.15nM(Bcr-AblQ252H),0.35nM(Bcr-AblH396P),0.29nM(Bcr-AblM351T),0.35nM(Bcr-AblY253F),Bcr-AblF317L[1]體外研究OlverembatinibdimesylateshowsantiproliferativeactivityinstablytransformedBa/F3cellswhosegrowthwasdrivenbynativeBcr-AblorBcr-Ablmutants[1].OlverembatinibdimesylateselectivelyandpotentlyinhibitstheproliferationofBcr-Abl-positiveleukemiacells[1].OlverembatinibdimesylateinhibitsBcr-AblsignalinginK562(1-20nM;4.0hours)andBa/F3stablecelllinesexpressingnativeBcr-Abl(0.1-100nM;4.0hours)orBcr-AblT315I(0.1-100nM;4.0hours)[1].WesternBlotAnalysis[1]CellLine:K562cellsConcentration:1nM,2nM,5nM,10nM,20nMIncubationTime:4.0hoursResult:InhibitedBcr-AblsignalinginK562celllines.體內(nèi)研究OlverembatinibdimesylatesuppressestumorgrowthinmicebearingallograftedBa/F3cellsexpressingBcr-AblWT[1].Olverembatinibdimesylate(1-20mg/kg;i.g.;daily;for10days)significantlyincreasesthemediansurvivalofthemicebearingallograftedBa/F3cellsexpressingBcr-AblT315I[1].Olverembatinibdimesylateexhibitsagoodoralbioavailability(rat48.7%)andCmax(rat390.5μg/L)followingoraladministration(rat;25mg/kg)[1].Olverembatinibdimesylateexhibitsterminaleliminationhalf-lives(rat5.6h)duetohighplasmaclearance(rat1.7L/h/kg)followingintravenousadministration(rat5mg/kg)[1].AnimalModel:SCIDnudemice,bearingallograftedBa/F3cellsexpressingBcr-AblT315I[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:1mg/kg,2mg/kg,5.0mg/kg,10mg/kg,20mg/kgAdministration:Oralgavage,daily,for10daysResult:Efficientlyprolongedanimalsurvivalinanallograftleukemiatumormodel.AnimalModel:Rats[1]Dosage:5mg/kgfori.v.;25mg/kgfororal(PharmacokineticAnalysis)Administration:IntravenousinjectionandoraladministrationResult:Oralbioavailability(48.7%),Cmax(390.5μg/L),T1/2(5.6h).戶使?本產(chǎn)品發(fā)表的科研?獻?BiochimBiophysActa.2018May25;1865(9):1173-1186.?ResearchSquarePreprint.2021Oct.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RenX,PanX,ZhangZ,IdentificationofGZD824asanorallybioavailableinhibitorthattargetsphosphorylatedandnonphosphorylatedbreakpointclusterregion-Abelson(Bcr-Abl)kinaseandovercomesclinicallyacquiredmutation-inducedresistanceagainstMce