Description
JNJ-63533054 (1802326-66-4) is a potent and selective brain-penetrant GPR139 agonist (EC50=16 nM) an orphan G-protein-coupled receptor expressed in the CNS.1Tritium-labeled JNJ-63533054 binds to cell membranes expressing GPR139 and can be displaced by putative endogenous ligands.2Decreases compulsive-like alcohol drinking and hyperalgesia in alcohol-dependent rodents.3Suppresses morphine intake in a mouse self-administration model.4
Biochem/physiol Actions
JNJ-63533054 is a potent and selective agonist of the orphan receptor hGPR139, a GPCR receptor expressed in the brain in circumventricular regions of the habenula and septum. JNJ-63533054 has an EC50 value of 16 nM, crosses the blood-brain barrier, and is orally available.
References
[1] CURT A. DVORAK*. Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor[J]. ACS Medicinal Chemistry Letters, 2015, 6 9: 1015-1018. DOI:
10.1021/acsmedchemlett.5b00247[2] CHANGLU LIU. GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine.[J]. Molecular Pharmacology, 2015, 88 5: 911-925. DOI:
10.1124/mol.115.100412[3] JENNI KONONOFF. Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats.[J]. eNeuro, 2018. DOI:
10.1523/eneuro.0153-18.2018[4] DANDAN WANG. Genetic behavioral screen identifies an orphan anti-opioid system[J]. Science, 2019, 365 6459. DOI:
10.1126/science.aau2078
