title: KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases.
abstract: The reversible acetylation of lysines is one of the best characterized epigenetic modifications. Its involvement in many key physiological and pathological processes has been documented in numerous studies. Lysine deacetylases (KDACs) and acetyltransferases (KATs) maintain the acetylation equilibrium at histones but also many other proteins. Besides acetylation, also other acyl groups are reversibly installed at the side chain of lysines in proteins. Because of their involvement in disease, KDACs and KATs were proposed to be promising drug targets, and for KDACs, indeed, five inhibitors are now approved for human use. While there is a similar level of evidence for the potential of KATs as drug targets, no inhibitor is in clinical trials. Here, we review the evidence for the diverse roles of KATs in disease pathology, provide an overview of structural features and the available modulators, including those targeting the bromodomains of KATs, and present an outlook.
authors.affiliation: Institute of Pharmaceutical Sciences, University of Freiburg , Albertstraße 25, Freiburg 79104, Germany.
authors.forename: Roman P
authors.initials: RP
authors.lastname: Simon
authors.affiliation: Department of Pharmaceutical Chemistry, University Halle-Wittenberg , Halle/Saale 06120, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Robaa
authors.affiliation: Department of Pharmaceutical Chemistry, University Halle-Wittenberg , Halle/Saale 06120, Germany.
authors.forename: Zayan
authors.initials: Z
authors.lastname: Alhalabi
authors.affiliation: Department of Pharmaceutical Chemistry, University Halle-Wittenberg , Halle/Saale 06120, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Institute of Pharmaceutical Sciences, University of Freiburg , Albertstraße 25, Freiburg 79104, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D055808:Drug Discovery; D044127:Epigenesis, Genetic / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D054852:Small Molecule Libraries; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D008239:Lysine