GZD824-dimesylate-HQP1351-dimesylate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEGZD824dimesylateCat.No.:HY-15666ACASNo.:1421783-64-3Synonyms:HQP1351dimesylate分?式:C??H??F?N?O?S?分?量:724.77作?靶點(diǎn):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(shí)驗(yàn)DMSO:125mg/mL(172.47mM;Needultrasonic)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，并請注意儲備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.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);Clearsolution1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性GZD824dimesylate(HQP1351dimesylate)?種有?服活性的pan-Bcr-Abl抑制劑，除了抑制野?型Bcr-Abl(IC50=0.34nM)之外，對突變型Bcr-Abl也具有?泛的抑制活性并且對野?型。GZD824dimesylate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GZD824dimesylateshowsantiproliferativeactivityinstablytransformedBa/F3cellswhosegrowthwasdrivenbynativeBcr-AblorBcr-Ablmutants[1].GZD824dimesylateselectivelyandpotentlyinhibitstheproliferationofBcr-Abl-positiveleukemiacells[1].GZD824dimesylateinhibitsBcr-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GZD824dimesylatesuppressestumorgrowthinmicebearingallograftedBa/F3cellsexpressingBcr-AblWT[1].GZD824dimesylate(1-20mg/kg;i.g.;daily;for10days)significantlyincreasesthemediansurvivalofthemicebearingallograftedBa/F3cellsexpressingBcr-AblT315I[1].GZD824dimesylateexhibitsagoodoralbioavailability(rat48.7%)andCmax(i.v.1375.6μg/L;oral390.5μg/L)followingadministration(5mg/kgfori.v.;25mg/kgfororal)inrat[1].AnimalModel:SCIDnudemice,bearingallograftedBa/F3cellsexpressingBcr-AblT315I[1]Dosage:1mg/kg,2mg/kg,5.0mg/kg,10mg/kg,20mg/kgAdministration:Oralgavage,daily,for10daysResult:Efficientlyprolongsanimalsurvivalinanallograftleukemiatumormodel.AnimalModel:Rats[1]Dosage:5mg/kgfori.v.;25mg/kgfororal(PharmacokineticAnalysis)Administration:Intravenousinjectionandoraladministration2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEResult:Oralbioavailability(48.7%),Cmax(1375.6μg/Lfori.v.;390.5μg/Lfororal),T1/2(5.6hourfori.v.;10.6hoursfororal).?BiochimBiophysActa.2018May25;1865(9):1173-1186.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RenX,PanX,ZhangZ,IdentificationofGZD824asanorallybioavailableinhibitorthattargetsphosphorylatedandnonphosphorylatedbreakpointclusterregion-Abelson(Bcr-Abl)kinaseandovercomesclinicallyacquiredmutation-inducedresistanceagainstimatinib.JMedChem.2013Feb14;56(3):879-94.McePdfHeightCaution:Pro