Abstract
The histamine H4 receptor was first reported over ten years ago and has become an attractive target for the development of drugs for the treatment of inflammation, pruritus, allergy and asthma. The H4 receptor mediates chemotaxis and cytokine release of mast cells, eosinophils, monocytes, dendritic cells and T cells. In addition, histamine released from mast cells or from other cell types can influence T cell polarization via activation of the H4 receptor. The receptor also mediates T cell activity in vivo and has a proinflammatory effect not only in models of the innate immune response, but also in models of asthma and contact dermatitis, where it mainly affects T cell responses. Extensive medicinal chemistry and pharmacology efforts have led to the development of modulators with excellent potency and selectivity for the H4 receptor. This has enabled exploration of the role of the receptor in human disease and provided candidates for clinical investigation. Several compounds have reached the clinic including JNJ 39758979 that has progressed into phase II clinical trials. This talk will highlight recent clinical and preclinical data supporting a role for the H4 receptor in human disease, as well as some of the obstacles encountered when advancing compounds with a novel mechanism into clinical studies.
