Marimastat-BB2516-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMarimastatCat.No.:HY-12169CASNo.:154039-60-8Synonyms:BB2516;TA2516分⼦式:C₁₅H₂₉N₃O₅分⼦量:331.41作⽤靶点:MMP作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(301.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.0174mL15.0871mL30.1741mL5mM0.6035mL3.0174mL6.0348mL10mM0.3017mL1.5087mL3.0174mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(7.54mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.54mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.54mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Marimastat(BB2516)⼀种⼴谱的，具有⼝服活性的MMPs抑制剂，有效抑制MMP-9(IC50=3nM),MMP-1(IC50=5nM),MMP-2(IC50=6nM),MMP-14(IC50=9nM),MMP-7(IC50=13nM)，⽤于癌症的研究。Marimastat(BB2516)⼀种⾎管⽣成和转移抑制剂，限制⾎管的⽣长和⽣成。作为⼀种抗变形剂，Marimastat(BB2516)可以防⽌恶性细胞突破底膜[1][2]。IC50&TargetMMP-3MMP-1MMP-2MMP-143nM(IC50)5nM(IC50)6nM(IC50)9nM(IC50)MMP-713nM(IC50)体外研究Marimastat(BB2516)(1μM)showsinhibitionofvascularoutgrowth,andselectivelyaffectsangiogenesis[3].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•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