Zinc enzymes in medicinal chemistry

In humans, more than three hundred diverse enzymes that require zinc as an essential cofactor have been identified. These zinc enzymes have demonstrated different and important physiological functions and some of them have been considered as valuable therapeutic targets for drug discovery. Indeed, many drugs targeting a few zinc enzymes have been marketed to treat a variety of diseases. This review discusses drug discovery and drug development based on a dozen of zinc enzymes, including their biological functions and pathogenic roles, their best in class inhibitors (and clinical trial data when available), coordination and binding modes of representative inhibitors, and their implications for further drug design. The opportunities and challenges in developing zinc enzyme inhibitors for the treatment of human disorders are highlighted, too. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

In humans, over three hundred enzymes dependent on zinc have been identified, some of which are considered valuable targets for drug discovery. Many drugs targeting these zinc enzymes have been marketed for treating various diseases. This review discusses drug discovery and development based on zinc enzymes, including biological functions, pathogenic roles, inhibitors, binding modes, and challenges in developing zinc enzyme inhibitors for human disorders.