Entacapone

Potent FTO (fat mass and obesity-associated gene) inhibitor for in vivo studies. FTO belongs to the Fe2+ and alpha-ketoglutarate (alpha-KG)-dependent oxygenase family. It demethylates N6-adenosine-modified (m6A) sites and N6,2'-O-dimethyladenosine-modified (m6Am) sites of mRNA. With its demethylase activity, FTO regulates the expression of some uncharacterized genes. The transcription factor FOXO1 has been shown to be a substrate of FTO. FTO demethylated m6A sites on forkhead box protein O1 (FOXO1) mRNA to up-regulate FOXO1 expression, thereby modulating gluconeogenesis and thermogenesis explaining in part the function of FTO on metabolic disorders such as obesity and diabetes. Potent selective and reversible catechol-O-methyltransferase (COMT) inhibitor, an enzyme involved in the metabolism of catecholamine neurotransmitters and related drugs. Entacapone is selective for COMT over monoamine oxidase A (MAO-A) and MAO-B and phenolsulphotransferase M (PST-M) and PST-P (IC50s = >50 µM). It is used for the treatment of Parkinson's disease, administered concomittantly with levodopa and a decarboxylase inhibitor (e.g. carbidopa). Inhibits alpha-synuclein aggregation in an in vitro assay and blocks alpha-synuclein-induced cell death in PC-12 cells. Shown to uncouple oxidative phosphorylation and inhibit mitochondrial enzyme complexes I and IV. Antioxidant that can scavenge toxic HOCl and ONOO--species and inhibit oxidative stress-induced cell death.