Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMarimastatCat.No.:HY-12169CASNo.:154039-60-8Synonyms:BB2516;TA2516分?式:C??H??N?O?分?量:331.41作?靶點:MMP作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:100mg/mL(301.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.0174mL15.0871mL30.1741mL5mM0.6035mL3.0174mL6.0348mL10mM0.3017mL1.5087mL3.0174mL請根據產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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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儲存條件，適當保存；體內實驗的?作液，建議您現?現配，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沉淀、析出現象，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(7.54mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.54mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.54mM);ClearsolutionBIOLOGICALACTIVITY?物活性Marimastat(BB2516)?種?譜的，具有?服活性的MMPs抑制劑，有效抑制MMP-9(IC50=3nM),MMP-1(IC50=5nM),MMP-2(IC50=6nM),MMP-14(IC50=9nM),MMP-7(IC50=13nM)，?于癌癥的研究。Marimastat(BB2516)?種?管?成和轉移抑制劑，限制?管的?長和?成。作為?種抗變形劑，Marimastat(BB2516)可以防?惡性細胞突破底膜[1][2]。IC50&TargetMMP-3MMP-1MMP-2MMP-143nM(IC50)5nM(IC50)6nM(IC50)9nM(IC50)MMP-713nM(IC50)體外研究Marimastat(BB2516)(1μM)showsinhibitionofvascularoutgrowth,andselectivelyaffectsangiogenesis[3].體內研究Animalsreceivingchemoradiation+Marimastat(BB2516)(8.7mg/kg)havestatisticallysignificantdelayedgrowth,comparedtoanimalsreceivingchemoradiationalone.Marimastat(BB2516)mayworkincombinationwithchemotherapyandradiationtoinhibittumorgrowth[4].PROTOCOLKinaseAssay[1]Compounds1,2,7-9and11-16arepre-incubatedwithMMP-1orMMP-3(10nM)atdifferentconcentrations(0-10μM)inamixtureofTris-HCl(50mM,pH7.5),NaCl(150mM),CaCl2(10mM),NaN3(0.02%)andBrij-35(0.05%)for1hourat37°C.ResidualactivityismeasuredusingthefluorogenicMMPsubstrate(2μM)byfluorescenceincrease(emissionat393nmandexcitationat325nm)onafluorescenceplatereader.Thedataarefittedtothetightbindinginhibitorequation:v=[(E-I-k+[(E-I-k)2+4Ek]1/2)/(2E)],wherevisthevelocityofthereaction,Eistheenzymeconcentration,Iistheinitialinhibitorconcentration,andkistheapparentinhibitionconstant,usingthesoftwarePrism.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalThree-month-oldfemalenudemiceareinoculatedusingatrocharneedlewith2mm2establishedSCC-1Administration[3]tissuesubcutaneouslyintheflank.Treatmentstartedoncethetumorsare5-6mmindiameter.MicearerandomLydividedintogroupsof8micetoreceivedifferenttreatments:(1)control,(2)marimastatalone,(3)cisplatin+radiationincombinationand(4)marimastat+cisplatin+radiationincombination.Allanimalsreceivea14-dayosmoticpumpcontainingdimethylsulfoxide(DMSO)asacontrolforboththepumpandvehicle.Animalstreatedwithmarimastatreceivethesameosmoticpumpcontaining200μLof2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEmarimastatwithDMSOtoresultinadailydoseof8.7mg/kg10daysaftertheinitiationoftreatment.Lead-shieldedanimalsreceive8Gyof60Coradiationtotheexposedtumor,dividedinto4fractionsondays8,12,16and20.Adoseof8Gyischosenbecause7.5Gy(7,500rad)hasbeenshowninpreviousexperimentstoinhibittumorgrowthwithoutbeingacurativedose.Animalsreceive4intraperitonealdosesofcisplatin(3mg/kg)1hbeforeeachfractionofradiation.Tumorsaremeasuredbiweeklyfor32days.Potentialtreatmenttoxicityismonitoredusingmouseweight.Tumorsize(surfaceareaequaltoproductoftwolargestdiameters)andregressionratesaredeterminedineachtreatmentgroup.After32days,tumorsareharvestedforimmunohistochemistry.Day32ischosenduetodeathofcontrolgroupanimalsandeuthanizationofanimalsshowingclinicalsignsofillnesstoallowforstatisticalanalysisofdataacquiredfromsurvivinganimals.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻?CellRes.2020Sep;30(9):779-793.?MolTher.2016Dec;24(12):2090-2099.?EMBORep.2021Jul5;22(7):e51678.?Viruses.2022,14(10),2094.?BioconjugChem.2016Dec21;27(12):2943-2953.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RasmussenHS,etal.Matrixmetalloproteinaseinhibitionasanovelanticancerstrategy:areviewwithspecialfocusonbatimastatandmarimastat.PharmacolTher.1997;75(1):69-75.[2].YuM,etal.IncorporationofBulkyandCationicCyclam-TriazoleMoietiesintoMarimastatCanGeneratePotentMMPInhibitoryActivitywithoutInducingCytotoxicity.ChemistryOpen.2013Jun;2(3):99-105.[3].vanWijngaardenJ,etal.Aninvitromodelthatcandistinguishbetweeneffectsonangiogenesisandonestablishedvasculature:actionsofTNP-470,marimastatandthetubulin-bindingagentAng-510.BiochemBiophysResCommun.2010Jan8;391(2):1161-5.[4].SkipperJB,etal.Invivoefficacyofmarimastatandchemoradiationinheadandneck