Abstract
The deorphanization of the histamine H₄ receptor (H₄R) has led to a significant number of scientific publications and patent applications. Whereas some histamine H₁, H₂ and H₃ receptor ligands were found to have significant affinity for H₄R, several agonists and antagonists with high affinity for H₄R and selectivity over the other histamine receptors were successfully designed and synthesized. Moreover, site-directed mutation studies on H₄R have been performed and reveal detailed information on receptor-ligand interactions. This review will focus on the most important H₄R ligand scaffolds and their structure-activity relationships and selectivity over other histamine receptors and specific H₄R functional activity. Experimental data are used to construct and validate high resolution three-dimensional receptor-ligand models and, vice versa, in silico models are used to design and rationalize experimental studies to probe receptor-ligand interactions.
Original language | English |
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Pages (from-to) | 661-79 |
Number of pages | 19 |
Journal | Current Topics in Medicinal Chemistry |
Volume | 11 |
Issue number | 6 |
Publication status | Published - 2011 |
Keywords
- Binding Sites
- Histamine Agonists
- Histamine Antagonists
- Humans
- Receptors, G-Protein-Coupled
- Receptors, Histamine
- Structure-Activity Relationship
- Journal Article
- Research Support, Non-U.S. Gov't
- Review