AMG-487-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAMG487Cat.No.:HY-15319CASNo.:473719-41-4分?式:C??H??F?N?O?分?量:603.59作?靶點:CXCR作?通路:GPCR/GProtein;Immunology/Inflammation儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥41mg/mL(67.93mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6568mL8.2838mL16.5675mL5mM0.3314mL1.6568mL3.3135mL10mM0.1657mL0.8284mL1.6568mL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。-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.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:≥2.5mg/mL(4.14mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(4.14mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.14mM);Clearsolution4.請依序添加每種溶劑：20%HP-β-CDinsalineSolubility:5mg/mL(8.28mM);Suspenedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性AMG487?種有效的、具有?服活性的、選擇性的趨化因?受體3(CXCR3)拮抗劑，抑制CXCL10和CXCL11與CXCR3結合的IC50值分別為8.0和8.2nM[1]。IC50&Target125I-IP10-CXCR3125I-ITAC-CXCR38nM(IC50)8.2nM(IC50)體外研究AMG487inhibitsCXCR3-mediatedcellmigrationbythethreeCXCR3chemokines(IP-10IC50=8nM,ITACIC50=15nM,andMIGIC50=36nM).Furthermore,AMG487inhibitscalciummobilizationinresponsetoITAC(IC50=5nM)[1].AMG487(1μM)developsintofewerlungmetastases,andthelungsaresignificantlysmallerthanvehicle-treatedlungs[2].AMG487abrogatesproliferation/survivalofC26tumourcells[3].體內(nèi)研究AMG487(0.03-10mg/kg,s.c.)exhibitssignificantreductionincellularinfiltrationintothelungsinadosedependentmanner[1].AMG487(5mg/kg,s.c.,twicedaily)developsfewermetastasesthanthatinvehicle-treatedmice[2].AMG487(5mg/kg,s.c.)-treatedmiceexhibitsfewerpulmonarynodulesthanthecontrolmiceinboththemodels.AMG487reducesthetumourvolume[3].PROTOCOLCellAssay[3]Coloncancercellsareseededatadensityof104cellscm2andincubatedeitherinserum-enrichedmediumorinbasemedium(containing0.1%bovineserumalbumin,BSA)supplementedornotwithvariousconcentrationsofrCXCL9,rCXCL10andrCXCL11fortheindicatedperiodsoftimebeforebeingeithertrypsin-detached,collectedandenumeratedorre-fedwithfreshmediumfor3days,harvestedandenumerated.ThemorphologyoftheCRCcellsisobservedthroughaninvertedopticalmicroscopeat×20magnification,andphotographsaretakenatday7.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalLocaltumorgrowthandspontaneousmetastasisareevaluatedbyinjecting3×105viabletumorcellss.c.Administration[2]proximaltotherightabdominalmammaryglandofsyngeneicfemalemice.Tumordiametersaremeasuredbycalipertwiceweekly,andmiceareeuthanizedonanindividualbasiswhenthes.c.tumormeasured18mmindiameterorearlierifthemouseseemedmoribund.Thelungsareremovedandweighed,andsurfacetumorcoloniesarequantifiedinablindedfashionunderadissectingmicroscope.Experimentalmetastasisisevaluatedbyinjecting9×104othelateraltailveinofsyngeneicfemalemice.Allmice2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEareeuthanizedonday21posttransplantationorearlierifthemiceseemedmoribund.Thelungsareremovedandweighed,andsurfacetumorcoloniesarequantifiedinablindedfashionunderadissectingmicroscope.A50%hydroxypropyl-β-cyclodextrinsolutionisprepared;at20%,thissolutionservesasthevehicle.AMG487isaddedtothe50%solution,anditisincubatedinasonicatingwaterbathfor2hourswithoccasionalvortexing.DistilledwaterisaddedtogivetheappropriatefinalconcentrationofAMG487in20%ofhydroxypropyl-β-cyclodextrin.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?AmJRespirCritCareMed.2022Oct15;206(8):981-998.?CellRep.2021Aug24;36(8):109613.?CancerLett.506(2021)95-106.?Oncogene.2022Mar;41(13):1866-1881.?FrontOncol.06August2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JohnsonM,etal.Discoveryandoptimizationofaseriesofquinazolinone-derivedantagonistsofCXCR3.BioorgMedChemLett.2007Jun15;17(12):3339-43.[2].WalserTC,etal.AntagonismofCXCR3inhibitslungmetastasisinamurinemodelofmetastaticbreastcancer.CancerRes.2006Aug1;66(15):7701-7.[3].CambienB,etal.Organ-specificinhibitionofmetastaticcoloncarcinomabyCXCR3antagonis