Mechanistic enzymology in drug discovery: a fresh perspective. Academic Article

abstract

• Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor and to inform the design of screens to identify desired mechanisms. Exploiting this information allows the thorough evaluation of diverse compounds, providing the knowledge required to efficiently optimize leads towards differentiated candidate drugs. This review highlights the rationale for conducting high-quality mechanistic enzymology studies and considers the added value in combining such studies with orthogonal biophysical methods.

authors

• Meek, Thomas

published proceedings

• Nat Rev Drug Discov

altmetric score

• 16.2

author list (cited authors)

• Holdgate, G. A., Meek, T. D., & Grimley, R. L.

citation count

• 88

complete list of authors

• Holdgate, Geoffrey A||Meek, Thomas D||Grimley, Rachel L

publication date

• January 2018

publisher

• Springer Nature  Publisher

published in

• Nature Reviews Drug Discovery  Journal

keywords

• 5 Development Of Treatments And Therapeutic Interventions
• 5.1 Pharmaceuticals

Digital Object Identifier (DOI)

• 10.1038/nrd.2017.219

start page

• 115

end page

• 132

volume

• 17

issue

• 2

URL

• http://dx.doi.org/10.1038/nrd.2017.219