JNJ-39758979

JNJ-39758979 is a selective, orally active, and high-affinity histamine H₄ receptor antagonist with K_is of 12.5, 5.3, and 25 nM for human, mouse, and monkey histamine H₄ receptor, respectively. JNJ-39758979 functionally antagonizes histamine-induced cAMP inhibition with a pA2 of 7.9 in transfected cells. JNJ-39758979 shows good anti-inflammatory and antipruritic activity^[1][2]. IC50 & Target: Ki: 12.5 nM (human histamine H₄ receptor), 5.3 nM (mouse histamine H₄ receptor), 25 nM (monkey 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 versus the human H₄ receptor and functionally antagonizes histamine-induced cAMP inhibition with a pA2 of 7.9 in transfected cells. At the mouse H₄R, the K_i=5.3 nM and the pA2=8.3. At the monkey H₄R, the K_i=25 nM and the pA2=7.5. The affinity for the rat (K_i=188 nM, pA2 = 7.2) 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). The compound is highly selective for H₄R, as it exhibits low affinity for the H₁, H₂, and H₃ receptors^[1].
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 (10 mg/kg; p.o.) treatment shows that the C_max, t_1/2 and F values are 0.3 μM, 7.5 hours, and 36%, respectively^[1].
JNJ-39758979 (2 mg/kg; i.v.) treatment shows that the Vss, AUC, CL and t_1/2 were 19.9 L/kg, 1.4 μM*h, 2.2 L/h, and 2.1 hours, respectively ^[1].