tcsc0020957 JNJ-39758979

JNJ-39758979 is a selective, high-affinity histamine H₄ receptor antagonist with a K_i of 12.5 nM.

IC50 & Target: Ki: 12.5 nM (histamine H₄ receptor)^[1]

In Vitro: JNJ-39758979 is a selective, high-affinity histamine H₄ receptor antagonist with a K_i of 12.5 nM.

The affinity of JNJ-39758979 for the rat (K_i=188 nM) and guinea pig H₄R (K_i=306 nM) is moderate, and JNJ-39758979 has little if any affinity for the dog H₄R (K_i≥10 μM). JNJ-39758979 is metabolically stable (t_1/2 >120 min) when incubated in vitro with human, rat, dog, or monkey liver microsomes^[1].

In Vivo: JNJ-39758979 shows dose-proportional pharmacokinetic (PK) in rat in the range of 2 to 500 mpK. JNJ-39758979 rapidly reaches the kidneys and liver (mean t_max=2.0 h). The elimination of JNJ-39758979 is slow from the brain, liver, and kidneys, with mean t_1/2 values of 42.5, 22.3, and 20.5 h, respectively. The highest exposure (based on C_max and AUC_0-inf values) is observed in the liver followed by the kidney and brain. Tissue-to-plasma ratios for liver and kidney range from 23.2 to 95.8; the tissue-to-plasma ratios in brain increases with time from 0.256 to 22.7 up to 48 h after dosing. JNJ-39758979 is able to inhibit histamine-induced itch at doses of 5 and 20 mg/kg in mice. JNJ-39758979 exhibits dose-dependent inhibition of the clinical score in a mouse collagen-induced arthritis model^[1].