Molecular Determinants of Selective Agonist and Antagonist Binding to the Histamine H-4 Receptor

作者：Istyastono Enade P; de Graaf Chris; de Esch Iwan J P; Leurs Rob^*

来源：Current Topics in Medicinal Chemistry, 2011, 11(6): 661-679.

• Histamine H-4
• structure-activity relationships
• site-directed mutations
• receptor-ligand interactions

The deorphanization of the histamine H-4 receptor (H4R) has led to a significant number of scientific publications and patent applications. Whereas some histamine H-1, H-2 and H-3 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.

• 出版日期2011-3