AZD7507-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZD7507Cat.No.:HY-117244CASNo.:1041852-85-0分⼦式:C₂₃H₂₇FN₆O₃分⼦量:454.5作⽤靶点:c-Fms作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:130mg/mL(286.03mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2002mL11.0011mL22.0022mL5mM0.4400mL2.2002mL4.4004mL10mM0.2200mL1.1001mL2.2002mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.17mg/mL(4.77mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.77mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AZD7507为⼀种有效的、可⼝服的CSF-1R抑制剂，具有抗肿瘤活性。IC50&TargetCSF-1R[1]体外研究AZD7507(Compound31)inhibitstheproliferationof3T3cellsengineeredtoexpressCSF-1RandstimulatedwithCSF-1(IC50,32nM),showsinhibitoryactivityagainsthERGandNaV1.5,withIC50sof>30and26μM[1].体内研究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—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbee