AZD7507-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAZD7507Cat.No.:HY-117244CASNo.:1041852-85-0分?式:C??H??FN?O?分?量:454.5作?靶點(diǎn):c-Fms作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:130mg/mL(286.03mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2002mL11.0011mL22.0022mL5mM0.4400mL2.2002mL4.4004mL10mM0.2200mL1.1001mL2.2002mL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(chǔ)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(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)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(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.17mg/mL(4.77mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.77mM);ClearsolutionBIOLOGICALACTIVITY?物活性AZD7507為?種有效的、可?服的CSF-1R抑制劑，具有抗腫瘤活性。IC50&TargetCSF-1R[1]體外研究AZD7507(Compound31)inhibitstheproliferationof3T3cellsengineeredtoexpressCSF-1RandstimulatedwithCSF-1(IC50,32nM),showsinhibitoryactivityagainsthERGandNaV1.5,withIC50sof>30and26μM[1].體內(nèi)研究AZD7507hasgoodratoralPK,withinvivoclearanceof7mL/min/kgand42%bioavailability.InthecanineL-typeCachannelassay,theIC50is>20μM[1].AZD7507significantlydecreasesthenumberofCD68+macrophagesinmice,andalsoreducesthevolumeandmassinmicebearingCC-LP-1andSNU-1079cells,butnotWITT-1cells[2].PROTOCOLAnimalMice[2]Administration[2]MaleCD1nudemiceareinjectedsubcutaneouslywith5×105humanICCcellsfromhumancelllineWITT-1,CC-LP-1,orSNU-1079(n=24inallcases)suspendedinculturemedia/RGFMatrigel(Gibco)mix(1:1).Cellsareengraftedbilaterallyintheflankandallowedtoformtumorsover3weeks.Oncepalpabletumorshaveformed,micearerandomizedinto3groupsusingGraphPadonlinesoftware.Xenograftedmiceareinjectedwithliposomalclodronateat4μL/gintravenously.Thecontrolforthistreatmentissalinealoneorliposomesnotcontainingclodronate(bothgivenat4μL/gintravenously).Allofthesetreatmentsaregivenevery48hoursfor3weeks.CSFR1inhibitorsAZD7507andGW2580aremadeupinsterilewatercontaining0.5%methylcelluloseand0.1%Tween-80.AZD7507isgiventwicedailyat100mg/kg,whereasGW2580isgivendailyat160mg/kg.Controlanimalsaregivenwatercontaining0.5%methylcelluloseand0.1%Tween-80.ICG-001(5mg/kg)orC-59(20mg/kg)isgivenbyintraperitonealinjection.Thevehicleforthisisphysiologicalsaline.Controlanimalsaregivenvehiclealone.Inallcasesinhibitorsandvehiclearegiven3timesperweek[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].ScottDA,etal.MitigationofcardiovasculartoxicityinaseriesofCSF-1Rinhibitors,andtheidentificationofAZD7507.BioorgMedChemLett.2013Aug15;23(16):4591-6.[2].BoulterL,etal.WNTsignalingdrivescholangiocarcinomagrowthandcanbepharmacologicallyinhibited.SendtoJClinInvest.2015Mar2;125(3):1269-85.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbee