Tolcapone | COMT inhibitor / TTR aggregation inhibitor

Tolcapone (134308-13-7) is a catechol O-methyltransferase inhibitor (COMT), inhibiting both brain and peripheral enzymes.¹ Potent inhibitor of alpha-synuclein and beta-amyloid oligomerization and fibrillogenesis protecting against extracellular toxicity.² 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. Stabilizes TTR in mice and humans in vivo.³ Inhibits O-methylation of exogenous polyphenols such as EGCG.⁴ Cell permeable. Orally bioavailable.

References/Citations

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