Pharmacological Targeting of AMP-Activated Protein Kinase and Opportunities for Computer-Aided Drug Design

Marie Miglianico*, Gerry A. F. Nicolaes, Dietbert Neumann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Web of Science)

Abstract

As a central regulator of metabolism, the AMP-activated protein kinase (AMPK) is an established therapeutic target for metabolic diseases. Beyond the metabolic area, the number of medical fields that involve AMPK grows continuously, expanding the potential applications for AMPK modulators. Even though indirect AMPK activators are used in the clinics for their beneficial metabolic outcome, the few described direct agonists all failed to reach the market to date, which leaves options open for novel targeting methods. As AMPK is not actually a single molecule and has different roles depending on its isoform composition, the opportunity for isoform-specific targeting has notably come forward, but the currently available modulators fall short of expectations. In this review, we argue that with the amount of available structural and ligand data, computer-based drug design offers a number of opportunities to undertake novel and isoform-specific targeting of AMPK.
Original languageEnglish
Pages (from-to)2879-2893
JournalJournal of Medicinal Chemistry
Volume59
Issue number7
DOIs
Publication statusPublished - 14 Apr 2016

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