Sapitinib-AZD-8931-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESapitinibCat.No.:HY-13050CASNo.:848942-61-0Synonyms:AZD-8931分?式:C??H??ClFN?O?分?量:473.93作?靶點:EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥33mg/mL(69.63mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1100mL10.5501mL21.1002mL5mM0.4220mL2.1100mL4.2200mL10mM0.2110mL1.0550mL2.1100mL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(dāng)?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(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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:≥2.5mg/mL(5.28mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.28mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.28mM);ClearsolutionBIOLOGICALACTIVITY?物活性Sapitinib(AZD-8931)可逆的，ATP競爭型EGFR抑制劑，對EGFR，ErbB2和ErbB3的IC50值分別為4，3和4nM。IC50&TargetEGFRErbB2HER34nM(IC50)3nM(IC50)4nM(IC50)體外研究AZD8931showspotentinhibitoryeffectonerbB2intheligand-independentMCF-7cl24cells,withIC50of59nM[1].AZD8931(1μM)hasnosignificanteffectonEGFRexpressionlevel,butsignificantlyinhibitsphosphorylationofAktinatime-anddose-dependentmannerinbothSUM149andFC-IBC-02cells.AZD8931(0.01,0.1,1,or2μM)inhibitsproliferationandinducesapoptosisinhumanIBCcells[2].Atthecellularlevel,AZD8931inhibitsEGF-stimulatedphosphorylationofEGFRintheKBcellline(IC50:4nM)andheregulin-stimulatedphosphorylationofHER2(IC50:3nM)andHER3(IC50:4nM)intheMCF-7cellline.However,AZD8931exhibitsnoCYPP450inhibition(IC50>10μMagainst1A2,2C9,2C19,2D6,and3A4)[3].體內(nèi)研究AZD8931(6.25-50mg/kg,p.o.)significantlyinhibitsBT474c(breast),Calu-3(NSCLC),LoVo(colorectal),FaDu(SCCHN),andPC-9(NSCLC)tumorxenograftgrowth.AZD8931isactiveinxenografttumormodelsresponsivetoEGFRinhibitionalone(LoVoandPC-9)orEGFRorerbB2inhibition(BT474c,Calu-3,andFaDu).AZD8931causespharmacodynamicchangesinproliferationandapoptosismarkersinhumantumorxenograftmodels[1].AZD8931(25mg/kg,p.o.)significantlyinhibitsthegrowthofSUM149andFC-IBC-02cellsinvivoinSCIDmice[2].AZD8931displaysfavorableoralpharmacokineticsinratanddog(lowclearanceandgoodbioavailability)andlowhumanhepatocyteturnover(Clint<4.5μL/min/106cells).Innudemouseafteroraladministrationat50mg/kg,AZD8931showsimprovedexposure,andatat100mg/kgoraldoseoncedaily,itshowspotenttumorgrowthinhibitionactivityintheLoVomousexenograftmodel[3].PROTOCOLCellAssay[1]Cellsareincubatedfor96hwithasuitablerangeofconcentrationsofdrugtoensureaccurateestimationoftheinhibitorconcentrationrequiredtogive50%growthinhibition(GI50;typicallybetween0.001-10μM).Viablecellnumberisdeterminedby4hofincubationwithMTSColorimetricAssayreagentandabsorbancemeasuredat490nmonaspectrophotometer.Eachexperimentiscarriedoutintriplicateforeachdrugconcentrationanddataarepresentedasgeometricmeans.SensitivitygroupingsofGI50dataare7μM.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalSwissnude(nu/nugenotype)andseverecombinedimmunodeficientmiceareused.AZD8931,GW572016,Administration[1]andZD1839aresuspendedina1%(v/v)solutionofpolyoxyethylenesorbitanmonooleate(Tween80)indeionizedwater.AnimalsaregivenAZD8931(6.25-50mg/kg),GW572016(100mg/kg),ZD1839(100-150mg/kg),orvehiclecontrolonce(qd)ortwicedaily(bid)byoralgavage.Thedurationofeachstudyisdeterminedbytumorgrowthcharacteristics,withstudiesendingoncetumorsreach~1cm3.Tumorvolumeandpercentagetumorgrowthinhibitionarecalculatedandstatisticalanalysisofanychangeintumorvolumeiscarriedoutusingastandardttest(Pvalueoflowerthen0.05isconsideredtobestatisticallysignificant).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?JTranslMed.2021Jan23;19(1):43.?MolCancerRes.2019Jan;17(1):20-29.?MolPharmacol.2019Dec;96(6):862-870.?bioRxiv.October28,2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HickinsonDM,etal.AZD8931,anequipotent,reversibleinhibitorofsignalingbyepidermalgrowthfactorreceptor,ERBB2(HER2),andERBB3:auniqueagentforsimultaneousERBBreceptorblockadeincancer.ClinCancerRes.2010Feb15;16(4):1159-69.[2].MuZ,etal.AZD8931,anequipotent,reversibleinhibitorofsignalingbyepidermalgrowthfactorreceptor(EGFR),HER2,andHER3:preclinicalactivityinHER2non-amplifiedinflammatorybreastcancermodels.JExpClinCancerRes.2014May30;33:47.[3].BarlaamB,etal.DiscoveryofAZD8931,anEquipotent,ReversibleInhibitorofSignalingbyEGFR,HER2,andHER3Receptors.ACSMedChemLett.2013May31;4(8):742-6.[4].WangR,etal.EndothelialCellsPromoteColorectalCancerCellSurvivalbyActivatingtheHER3-AKTPathwayi