Background:

IC50: A Histamine H4 receptor antagonist with IC50 of 4.5 nM.

Histamine has been reported to play an important role in a large number of physiological processes. JNJ-7777120, the first potent and selective non-imidazole histamine H4 receptor antagonist with Ki of 4.5 nM, exhibits more than 1000-fold selectivity over the other histamine receptors. [1]

In vitro: It was reported that NJ 7777120 bound to the H4 receptor with a remarkably high affinity. It also demonstrated a greater selectivity over other histamine receptor antagonists. Moreover, JNJ 7777120 selectively targeted to potent H4 rather than 50 other molecular targets. [2]

In vivo: JNJ 7777120 showed an oral bioavailability of about 30% in rats and 100% in dogs, with a half-life of around 3 h in both rats and dogs. It was reported to inhibit histamine-induced chemotaxis and calcium influx in mouse bone marrow-derived mast cells. In addition, in mice, JNJ 7777120 could suppress the histamine-induced migration of tracheal mast cells from the connective tissue to the epithelium. Moreover, JNJ 7777120 was demonstrated to notably inhibit neutrophil infiltration in a mouse zymosan-induced peritonitis model. [2]

Clinical trial: So far, no clinical trial has been conducted.

参考文献:
[1]Jablonowski JA, Grice CA, Chai W, Dvorak CA, Venable JD, Kwok AK, Ly KS, Wei J, Baker SM, Desai PJ, Jiang W, Wilson SJ, Thurmond RL, Karlsson L, Edwards JP, Lovenberg TW and Carruthers NI.  The first potent and selective non-imidazole human histamine H4 receptor antagonists. J Med Chem. 2003 Sep; 46(19): 3957-60.
[2]Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, Williams KN, Edwards JP and Karlsson L.  A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther. 2004 Apr; 309(1): 404-13.