title: Inhibition of CatA: an emerging strategy for the treatment of heart failure.
abstract: The lysosomal serine carboxypeptidase CatA has a very important and well-known structural function as well as a, so far, less explored catalytic function. A complete loss of the CatA protein results in the lysosomal storage disease galactosialidosis caused by intralysosomal degradation of β-galactosidase and neuraminidase 1. However, mice with a catalytically inactive CatA enzyme show no signs of this disease. This observation establishes a clear distinction between structural and catalytic functions of the CatA enzyme. Recently, several classes of orally bioavailable synthetic inhibitors of CatA have been identified. Pharmacological studies in rodents indicate a remarkable influence of CatA inhibition on cardiovascular disease progression and identify CatA as a promising novel target for the treatment of heart failure.
authors.affiliation: SanofiDeutschland GmbH, Industriepark Höchst, 65926 Frankfurt, Germany. sven.ruf@sanofi.com
authors.forename: Sven
authors.initials: S
authors.lastname: Ruf
authors.forename: Christian
authors.initials: C
authors.lastname: Buning
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Linz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hübschle
authors.forename: Dominik
authors.initials: D
authors.lastname: Linz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Ruetten
authors.forename: Klaus
authors.initials: K
authors.lastname: Wirth
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sadowski
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D043402:Cathepsin A / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013379:Substrate Specificity
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D057786:Peptidomimetics; D054852:Small Molecule Libraries; D043402:Cathepsin A