Novel histamine H4 receptor ligands and their potential therapeutic applications: an update

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.