Methyltransferase (COMT) inhibitor. COMT (catechol O-methyltransferase) interacts with SARS-CoV-2 Nsp7; Tolcapone inhibits fevline coronavirus in cells. Gordon et al. bioRxiv, Mar 23 2020, https://doi.org/10.1101/2020.03.22.002386; Ke et al. Biomed. J., May 15 2020, https://doi.org/10.1016/j.bj.2020.05.001.
Biochemicals & reagents
1) Manisto et al. (1992), Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat; Br, J. Pharmacol., 105 569 2) Giovanni et al. (2010), Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity; J. Biol. Chem., 285 14941 3) Sant’Anna et al. (2016), Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity; Nat. Commun., 7 10787 4) Forester and Lambert (2015), The catechol-O-methyltranseferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice; Funct. Foods, 17 183
Tolcapone is a catechol O-methyltransferase inhibitor (COMT), inhibiting both brain and peripheral enzymes (1). This compound is a potent inhibitor of alpha-synuclein and beta-amyloid oligomerization and fibrillogenesis protecting against extracellular toxicity (2), also binds to transthyretin (TTR) with high affinity (21 to 58 nM) and inhibits TTR aggregation in human plasma and prevents TTR-induced cytotoxicity in vitro. It also stabilizes TTR in mice and humans in vivo (3), inhibits O-methylation of exogenous polyphenols such as EGCG (4), is cell permeable and orally bioavailable.