Histamine and its receptor
PHAR3014 Medicinal Chemistry & Drug Design
H4-receptor
The H4 subclass of histamine receptors mediates the histamine signal in peripheral tissues mainly regulating the level of white blood cells released from bone marrow. These receptors are widely distributed in the thymus, small intestine, spleen, colon, bone marrow, basophils and cells of hematopoietic origin. H4-R encodes a 390-amino acid Gi-coupled receptor with 40% homology to the H3-R and a similar intron-exon structure (Protein Data Bank, 2017).
VUF-6002 is the highly selective H4-R antagonist as it is orally active and inhibits the activity of mast cells and eosinophils in vivo at the same time provide effects on reducing inflammation and hyperalgesia. The agonists for this receptor are 4-methylhistamine and VUF-8430.
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However, the further molecular and biological understanding of this receptor is still undergoing trials and in the subject of investigation.
SAR
Glutamate present in the H4-R form an ionic interaction with the Nτ atom of histamine and its analogue.
Figure 19 Above, VUF-6002. Below, 4-methylhistamine and VUF-8430.
Figure 20 The binding interaction of histamine with glutamate side chain.