title: Discovering inhibitors of human sirtuin type 2: novel structural scaffolds.
abstract: A successful virtual screening experiment of novel SIRT2 inhibitors is described. Four out of 11 experimentally tested compounds showed in vitro inhibitory activity toward SIRT2 in a micromolar level, resulting in an experimental hit ratio of 36%. Two of these compounds inhibited SIRT2 with IC50 (microM) values of 51 and 91; moreover, one of the new inhibitors was comprised of an entirely new SIRT2-inhibiting structural scaffold.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, and Department of Neurology, Kuopio University Hospital, Post Office Box 1777, 70211 Kuopio, Finland.
authors.forename: Anu J
authors.initials: AJ
authors.lastname: Tervo
authors.forename: Tiina
authors.initials: T
authors.lastname: Suuronen
authors.forename: Sergiy
authors.initials: S
authors.lastname: Kyrylenko
authors.forename: Erkki
authors.initials: E
authors.lastname: Kuusisto
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Kiviranta
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Jukka
authors.initials: J
authors.lastname: Leppänen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
mesh_terms: D001559:Benzhydryl Compounds / Q000737:chemistry; D001562:Benzimidazoles / Q000737:chemistry; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry
chemical_list: D001559:Benzhydryl Compounds; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; D013844:Thiazoles; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins