Small-molecule inhibitors of NADPH oxidase 4.
NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
Borbély
Gábor
G
Vichem Chemie Research Ltd., Budapest, Hungary. gabor.borbely@kkk.org.hu
Szabadkai
István
I
Horváth
Zoltán
Z
Markó
Péter
P
Varga
Zoltán
Z
Breza
Nóra
N
Baska
Ferenc
F
Vántus
Tibor
T
Huszár
Mónika
M
Geiszt
Miklós
M
Hunyady
László
L
Buday
László
L
Orfi
László
L
Kéri
György
G
D000636:Aminosalicylic Acids / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010070:Oxalates / Q000737:chemistry / Q000494:pharmacology; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000636:Aminosalicylic Acids; D005419:Flavonoids; D007211:Indoles; D010070:Oxalates; D010616:Phenanthrenes; D011743:Pyrimidines; D006861:Hydrogen Peroxide; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human