Allosteric targeting of receptor tyrosine kinases

Frederik De Smet, Arthur Christopoulos, Peter Carmeliet

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

Abstract

The drug discovery landscape has been transformed over the past decade by the discovery of allosteric modulators of all major mammalian receptor superfamilies. Allosteric ligands are a rich potential source of drugs and drug targets with clear therapeutic advantages. G protein?coupled receptors, ligand-gated ion channels and intracellular nuclear hormone receptors have all been targeted by allosteric modulators. More recently, a receptor tyrosine kinase (RTK) has been targeted by an extracellular small-molecule allosteric modulator. Allosteric mechanisms of structurally distinct molecules that target the various receptor families are more alike than originally anticipated and include selectivity, orthosteric probe dependence and pathway-biased signaling.
Original languageEnglish
Pages (from-to)1113 - 1120
Number of pages8
JournalNature Biotechnology
Volume32
Issue number11
DOIs
Publication statusPublished - 2014

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