title: A highly soluble matrix metalloproteinase-9 inhibitor for potential treatment of dry eye syndrome.
abstract: Dry eye syndrome (DES) or keratoconjunctivitis sicca is an eye disease caused by the chronic lack of lubrication and moisture of the eye. The pathogenesis of DES involves the over-expression and over-activity of corneal Matrix Metalloproteinase 9 (MMP-9). We propose herein a new, non-symptomatic approach for the treatment of DES based on the inhibition of MMP-9 by a new highly soluble molecule, designed as PES_103 that has been shown to inhibit MMP-9 both in vitro and in vivo. The efficacy of PES_103 in vivo and the potential benefits of this treatment in restoring tear production were studied in this work using an animal model of reduced lacrimation. PES_103 did not show any significant corneal toxicity.
authors.affiliation: ProtEra Srl, Scientific Campus of the University of Florence, Florence, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Mori
authors.forename: Emanuele
authors.initials: E
authors.lastname: De Lorenzo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Torre
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Annarosa
authors.initials: A
authors.lastname: Arcangeli
mesh_terms: D000818:Animals; D002460:Cell Line; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009883:Ophthalmic Solutions; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012995:Solubility; D013449:Sulfonamides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013666:Tears / Q000201:enzymology
chemical_list: C578676:2-((2,3-dihydroxypropyl)((4-methoxyphenyl)sulfonyl)amino)-N-hydroxyacetamide; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D009883:Ophthalmic Solutions; D011994:Recombinant Proteins; D013449:Sulfonamides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9