Discovering inhibitors of human sirtuin type 2: novel structural scaffolds.
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.
Tervo
Anu J
AJ
Department of Pharmaceutical Chemistry, University of Kuopio, and Department of Neurology, Kuopio University Hospital, Post Office Box 1777, 70211 Kuopio, Finland.
Suuronen
Tiina
T
Kyrylenko
Sergiy
S
Kuusisto
Erkki
E
Kiviranta
Päivi H
PH
Salminen
Antero
A
Leppänen
Jukka
J
Poso
Antti
A
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
D001559:Benzhydryl Compounds; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; D013844:Thiazoles; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins