Lucitanib-dihydrochloride-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELucitanibdihydrochlorideCat.No.:HY-15391ACASNo.:2108875-91-6分⼦式:C₂₆H₂₇Cl₂N₃O₄分⼦量:516.42作⽤靶点:VEGFR;FGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Lucitanib(E-3810)dihydrochlorideVEGFR和FGFR的双重抑制剂，有效和选择性地抑制VEGFR1，VEGFR2，VEGFR3，FGFR1，FGFR2，IC50分别为7nM，25nM，10nM，17.5nM，82.5nM。IC50&TargetVEGFR1VEGFR2VEGFR3FGFR17nM(IC50)25nM(IC50)10nM(IC50)17.5nM(IC50)FGFR282.5nM(IC50)体外研究ConsistentwiththeinhibitoryactivityofVEGFRandFGFRauto-phosphorylation,LucitanibpotentlyinhibitsVEGFandbFGF-stimulatedHUVECproliferationwithIC50of40and50nM,respectively.Besides,Lucitanib(E-3810)alsoinhibitsCSF-1RwithIC50of5nM[1].LucitanibpotentlyinhibitsFGFR2activity(Kii=0.11μM).TheKivaluesobtainedforDDR2,LYN,CARDIAK,CSBP(2),EPHA2,andYESrangebetween0.26and8μM[2].体内研究Lucitanib(E-3810),atoraldosingof20mg/kgfor7consecutivedays,completelyinhibits(P[1].TheactivityofLucitanib(E-3810)givenatthedosesof15mg/kgistestedonMDA-MB-231breastcancertransplantedsubcutaneously,atalatestage,whentumormassesreach350to400mg.ThistumorxenograftisverysensitivetoLucitanib(E-3810),withcompletetumorstabilizationlastingthroughoutthe30-daytreatment.Asinothertumormodels,tumorsre-growafterwithdrawalofLucitanib(E-3810)ataratesimilartocontroltumors[3].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEPROTOCOLCellAssay[1]ExponentiallygrowingHUVECorNHI3T3cellsareseededinto96-wellplatesatadensityof3to6×103cells/100μL/wellincompletemedium.Intheexperimentswithoutserumstarvation,24hoursafterseeding,cellsareexposedtodifferentLucitanib(E-3810)concentrationswithoutorwithVEGF165(50ng/mL)orbFGF(20ng/mL)ligandsandtheantiproliferativeeffectofthedrugsisevaluatedafter72hoursbyMTSColorimetricAssay.Intheassayswithserumstarvationconditions,24hoursafterseedingcompletemediumisremovedandafter3roundsofwashingwithPBS,cellsareculturedinmediumcontaining1%BSA.After18to24hours,cellsareprocessed.ExponentiallygrowingA2780,A498,SN12KI,andHepG2cellsareseededinto96-wellplatesat3to5×103cells/100μL/wellincompletemedium.Twenty-fourhourslatercellsaretreatedwithdifferentdrugconcentrationsfor72hoursandtheantiproliferativeeffectisevaluatedbyMTS[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[2]MDA-MB-231tumor-bearingmicearerandomizedwhentheirtumormassesareabout350to400mgtoreceiveLucitanib(E-3810)(15mg/kg),Brivanib,andSU11248atthedosesusedfortheantitumoractivitytrial,for10days.Fourhoursaftertheantiangiogenicdoseofday7,NSC125973isinjectedintravenouslyatthedoseof20mg/kgandtumorandplasmasamplesarecollectedafter1,4,and24hoursinallthegroups(eachgroupconsistingof3animals).Attheindicatedsamplingtime,miceareanesthetized,bloodiscollectedfromtheretro-orbitalplexusintoheparinizedtubes,andtheplasmafractionisseparated.Micearekilledbycervicaldislocation,andtumorsexcisedandsnap-frozen.Thesamplesareanalyzedbyhigh-performanceliquidchromatography(HPLC)withUVdetectionat230nm.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.•Science.2017Dec1;358(6367):eaan4368.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•MolSystBiol.2023Dec18.•Oncogene.2022Dec13.•MolCancerTher.2019Jan;18(1):28-38.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BelloE,etal.E-3810isapotentdualinhibitorofVEGFRandFGFRthatexertsantitumoractivityinmultiplepreclinicalmodels.CancerRes.2011Feb15;71(4):1396-405.[2].ColzaniM,etal.Quantitativechemicalproteomicsidentifiesnoveltargetsoftheanti-cancermulti-kinaseinhibitorE-3810.MolCellProteomics.2014Jun;13(6):1495-509.[3].BelloE,etal.ThetyrosinekinaseinhibitorE-3810combinedwithNSC125973inhibitsthegrowthofadvanced-stagetriple-negativebreastcancerxenografts.MolCancerTher.2013Feb;12(2):131-40McePdfHeight2/2MasterofBioactiveMolecule