Dopamine β hydroxylase as a potential drug target to combat hypertension. (1st September 2020)

• Record Type: Journal Article
• Authors: Dey, Sanjay Kumar; Saini, Manisha; Prabhakar, Pankaj; Kundu, Suman
• Is Part Of: Expert opinion on investigational drugs. Volume 29:Number 9(2020)
• Page Start: 1043
• Page End: 1057
• Publication Date: 2020-09-01
• Subjects: Cardiovascular disorders -- catecholamines -- computer-aided structure-based drug design -- dopamine β hydroxylase -- drug target -- hypertension; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2020.1795830
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction: Despite a large number of commercially available drugs, hypertension and related cardiovascular diseases remain a global problem. It is thus imperative that novel drugs and therapeutic strategies are regularly identified, and alternative targets explored. Dopamine β hydroxylase (DBH), a key player in the catecholamine biosynthetic pathway, may provide a therapeutic opportunity and should be extensively explored as a target for potent anti-hypertensives. Inhibitors of DBH have been successful in combating hypertension, as evidenced by the outcome of clinical trials for etamicastat and zamicastat. Areas covered: We shed light on the strategies employed to identify inhibitors of the enzyme and outline the advantages that the target might offer. Structural and functional details of the enzyme are described along with specific methodologies for drug discovery that were never utilized for the therapeutic target. Expert opinion: Effective inhibitors of the enzyme may be identified with computer-aided structure-based design. Adoption of new methodologies and the assessment of newly designed inhibitors in DBH-specific animal models will provide new, safe, and cost-effective therapeutic opportunities.