JNJ7777120

JNJ7777120 is a potent and selective small molecule antagonist of the histamine H4 receptor (H4R), with a Ki of approximately 4.5 nM[1][9]. Developed by Johnson & Johnson Pharmaceutical Research & Development, it was the first non-imidazole H4R antagonist and exhibits over 1000-fold selectivity for H4R compared to other histamine receptors[9]. Preclinical studies demonstrated anti-inflammatory effects superior to traditional H1 antihistamines in models of pruritus (itching), as well as efficacy in reducing inflammation, neurotoxicity, and behavioral deficits in animal models of depression, allergic rhinitis, traumatic brain injury, and Parkinson’s-like pathology[2][3][5][6]. Mechanistically, it blocks histamine-induced migration of immune cells such as mast cells and microglia; its antagonism at the H4 receptor modulates immune responses by inhibiting pro-inflammatory signaling pathways including ERK1/2/NF-κB[1][6]. Despite its utility as a pharmacological tool compound for elucidating the role of H4R in inflammation and neuroimmune interactions, development was discontinued due to short in vivo half-life and hypoadrenocorticism toxicity observed in preclinical species (rats/dogs)[7][8].

Other names

1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine