GPR139 is an orphan G-protein–coupled receptor enriched in the Habenula and Septum. JNJ-63533054 is a potent, selective, small-molecule GPR139 agonist. It activated human GPR139 in the calcium mobilization and GTPgS binding assays with EC50 values of 16±6 and 17±4nM, respectively. JNJ-63533054 also activated rat and mouse GPR139 receptors with EC50 values of 63±24 and 28±7nM, respectively. The inhibition equilibrium constants (Ki) of JNJ-63533054 for binding to the membrane of cells expressing human, rat or mouse GPR139 are 23±3, 75±25, 54±12nM, respectively. L-Trp and L-Phe competed for [3H]JNJ-63533054 binding sites in T-REx CHO cells expressing human GPR139 with Ki values of 738±64 and 872±7μM, respectively. In Sprague-Dawley rats, JNJ-63533054 at dosages of 3, 10, and 30mg/kg induced a dose-dependent reduction in locomotor activity in the first hour after the treatment when compared with the vehicle-treated group[3].
作用机制
JNJ-63533054 is a potent agonist of GPR139, an orphan G protein-coupled receptor expressed in the central nervous system[3].
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