Cruz-Vicente, PedroGonçalves, Ana M.Barroca-Ferreira, JorgeSilvestre, Samuel M.Romão, Maria J.Queiroz, João A.Gallardo, EugéniaPassarinha, Luís A.2023-10-062023-10-062022-101359-6446PURE: 55867393PURE UUID: d36a48d0-849d-44ee-9919-fc23f0ed7e59Scopus: 85135397812PubMed: 35907613WOS: 000862832600021http://hdl.handle.net/10362/158732Funding Information: The authors acknowledge support from FEDER funds through the POCI – COMPETE 2020 – Operational Programme Competitiveness and Internationalisation in Axis I – Strengthening Research, Technological Development and innovation (Project POCI-01-0145-FEDER-007491). Publisher Copyright: © 2022 Elsevier LtdCatechol-O-methyltransferase (COMT) is an enzyme responsible for the O-methylation of biologically active catechol-based molecules. It has been associated with several neurological disorders, especially Parkinson's disease (PD), because of its involvement in catecholamine metabolism, and has been considered an important therapeutic target for central nervous system disorders. In this review, we summarize the biophysical, structural, and therapeutical relevance of COMT; the medicinal chemistry behind the development of COMT inhibitors and the application of computer-aided design to support the design of novel molecules; current methodologies for the biosynthesis, isolation, and purification of COMT; and revise existing bioanalytical approaches for the assessment of enzymatic activity in several biological matrices.15461021engBioanalytical methodsCatechol-O-methyltransferaseComputer-aided drug designCOMT inhibitorsUp-/down-stream processingPharmacologyDrug Discoveryreview10.1016/j.drudis.2022.07.013https://www.scopus.com/pages/publications/85135397812