Introduction: Histamine H4 receptor (H4R) has been shown to be involved in various inflammatory conditions. Ligands acting on H4R show therapeutic potential in various diseases. For the first time, the positive proof-of-concept clinical trials of the H4 antagonist JNJ39758979 have demonstrated this potential in histamine-induced pruritus. Besides role of H4R in inflammatory conditions, preclinical results in cancer, neuropathic pain, vestibular disorders and type 2 diabetes show the diverse signaling network modulated by H4R. This suggests further potential for H4 ligands in such diseases.
Areas covered: In this review, we have summarized patent applications and papers of the H4R field published between 2012 and 2014. Additionally, we have analyzed the quality of the already described H4 ligands in terms of their ligand efficiency, lipophilic ligand efficiency and lipophilicity-corrected ligand efficiency.
Expert opinion: We demonstrate that the number of published patent applications reached a maximum in 2009 and showed some decrease in the last few years. On the other hand, the field is still very lively, reflected by the numerous publications on novel potential therapeutic applications. The favorable property profile of H4 ligands in development shows promise for the upcoming human clinical trials.
Keywords: H4 antagonist; H4 receptor; JNJ39758979; JNJ7777120; histamine.