Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECilengitideTFACat.No.:HY-16143CASNo.:199807-35-7Synonyms:EMD121974TFA分?式:C??H??F?N?O?分?量:702.68作?靶點(diǎn):Integrin;Autophagy作?通路:Cytoskeleton;Autophagy儲(chǔ)存?式:-20°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)H2O:25mg/mL(35.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.4231mL7.1156mL14.2312mL5mM0.2846mL1.4231mL2.8462mL10mM0.1423mL0.7116mL1.4231mL請(qǐng)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(qǐng)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(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。BIOLOGICALACTIVITY?物活性Cilengitide有效的，選擇性的αvβ3和αvβ5受體整合素抑制劑，IC50分別為4nM和79nM。IC50&TargetIC50:4/79nM(αvβ3/αvβ5)[1].體外研究Cilengitide(EMD121974)istheαvβ3andαvβ5integrinreceptorantagonist.Incelladhesionstudies1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEassessingthehumanmelanomaM21orUCLA-P3humanlungcarcinomacelllines,Cilengitideinhibitsintegrin-mediatedbindingtovitronectinwithIC50sof0.4and0.4μM[1].InvitrotreatmentofCilengitide,ataconcentrationgreaterthan1μM,showsconcentration-andtime-dependentcytotoxiceffects[2].體內(nèi)研究InnudemicebearingM21-Lmelanomatumors,Cilengitidedosei.p.at10,50,and250μgthreetimesperweekdemonstrateinhibitionoftumorgrowthwithareductioninbothtumorvolume(55%,75%,and89%,respectively)andtumorweight(23%,38%,and61%,respectively),whencomparedtocontrols[2].Intheratmodelstudied,thesystemicpharmacokineticsofi.p.CilengitidearenotaffectedbyILPwithCilengitidealoneorILPwithCilengitideplusMelphalan,TNForboth.SystemicCilengitidelevelsreacharound20μg/mL(approximately35μM)within10minofi.p.administrationandcontinuedtorisetoapproximately40μg/mL(approximately70μM)inthefirsthour.ThereafterCilengitidelevelsinserumdropwithaneliminationhalf-lifeof2.1hr[3].PROTOCOLCellAssay[2]Thecytotoxicityofthetwodrugs,BelotecanandCilengitide,ismeasuredbytheCellCountingKit-8(CCK-8).U87MGandU251MGcellsareseededin96wellplatesatadensityof4×103cellsperwelltoallowforadhesionovernight.Afterthis,thecellsaretreatedwithCilengitideataconcentrationof0,0.1,0.5,1,5and25μMandBelotecanataconcentrationof0,6.25,12.5,25,50and100nM.AllpossiblecombinationsofconcentrationsareusedtoassessthecombinedtherapeuticeffectofCilengitideandBelotecan.After3days,10μLoftheCCK-8solutionisaddedtoeachwelloftheplate,andtheplateisincubatedfor3hrintheincubator(37°C;5%CO2)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2][3]MaleBalb/c-numice,at8weeksofage,arerandomlyassignedtofourgroups:control(n=10),Cilengitide(n=10),Belotecan(n=10)andcombination(n=10).Cilengitideisadministeredintraperitoneallyatadoseof20mg/kgdailyandtheBelotecanatadoseof10mg/kgevery4days.Thedrugtreatmentsbegan7daysaftertheimplantationoftumorcellsfor16days.Halfoftheanimalsaresacrificed1monthaftertheimplantationofthetumorcellsfortumorvolumeanalysisandtherestoftheanimalsareobservedforanother2monthstoanalyzesurvival.Thedeathoftheanimalsisdefinedasaweightreductionofover25%oftheinitialweightoranunexpectedsuddendeathbeforehand[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2020Aug6;182(3):545-562.e23.?CancerCell.2021Sep28;S1535-6108(21)00492-X.?NatCellBiol.2020Mar;22(3):289-296.?Engineering.8October2020.?JImmunotherCancer.2020Mar;8(1):e000111.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].HariharanS,etal.Assessmentofthebiologicalandpharmacologicaleffectsofthealphanubeta3andalphanubeta5integrinreceptorantagonist,Cilengitide(EMD121974),inpatientswithadvancedsolidtumors.AnnOncol.2007Aug;18(8):1400-7.[2].KimYH,etal.Combinationtherapyofcilengitidewithbelotecanagainstexperimentalglioblastoma.IntJCancer.2013Aug1;133(3):749-56.[3].TenHagenTL,etal.TheαVβ3/αVβ5integrininhibitorcilengitideaugmentstumorresponsetomelphalanisolatedlimbperfusioninasarcomamodel.IntJ