GPR139 explained

G-protein coupled receptor 139 (GPC139) is a protein that in humans is encoded by the GPR139 gene.^{[1] [2]} Research has shown that mice with loss of GCP139 experience schizophrenia-like symptomatology that is rescued with the dopamine receptor antagonist haloperidol and the μ-opioid receptor antagonist naltrexone.^{[3] [4]}

Ligands

Agonists

• Zelatriazin (TAK-41), (NBI-1065846) a potent, and GPR139 receptor selective agonist ^[5] which was in clinical trials to gauge the efficacy for treating psychiatric conditions such as major depressive disorder and the negative symptoms of schizophrenia, but was later dropped from development.

Antagonists

• JNJ-3792165

Further reading

• Vanti WB, Nguyen T, Cheng R, Lynch KR, George SR, O'Dowd BF . Novel human G-protein-coupled receptors . Biochemical and Biophysical Research Communications . 305 . 1 . 67–71 . May 2003 . 12732197 . 10.1016/S0006-291X(03)00709-5 .
• Ottolenghi C, Fellous M, Barbieri M, McElreavey K . Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination . Genomics . 79 . 3 . 333–343 . March 2002 . 11863363 . 10.1006/geno.2002.6711 .
• Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S . Identification of G protein-coupled receptor genes from the human genome sequence . FEBS Letters . 520 . 1–3 . 97–101 . June 2002 . 12044878 . 10.1016/S0014-5793(02)02775-8 . 7116392 .
• Gloriam DE, Schiöth HB, Fredriksson R . Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship . Biochimica et Biophysica Acta (BBA) - General Subjects . 1722 . 3 . 235–246 . April 2005 . 15777626 . 10.1016/j.bbagen.2004.12.001 .
• Matsuo A, Matsumoto S, Nagano M, Masumoto KH, Takasaki J, Matsumoto M, Kobori M, Katoh M, Shigeyoshi Y . 6 . Molecular cloning and characterization of a novel Gq-coupled orphan receptor GPRg1 exclusively expressed in the central nervous system . Biochemical and Biophysical Research Communications . 331 . 1 . 363–369 . May 2005 . 15845401 . 10.1016/j.bbrc.2005.03.174 .

Notes and References

1. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA . 6 . The G protein-coupled receptor repertoires of human and mouse . Proceedings of the National Academy of Sciences of the United States of America . 100 . 8 . 4903–4908 . April 2003 . 12679517 . 153653 . 10.1073/pnas.0230374100 . free . 2003PNAS..100.4903V .
2. Web site: Entrez Gene: GPR139 G protein-coupled receptor 139.
3. Dao M, Stoveken HM, Cao Y, Martemyanov KA . The role of orphan receptor GPR139 in neuropsychiatric behavior . Neuropsychopharmacology . 47 . 4 . 902–913 . March 2022 . 33479510 . 10.1038/s41386-021-00962-2 . 8882194 . 231668867 .
4. Vedel L, Nøhr AC, Gloriam DE, Bräuner-Osborne H. Pharmacology and function of the orphan GPR139 G protein-coupled receptor. Basic Clin Pharmacol Toxicol. 2020 Jun;126 Suppl 6(Suppl 6):35-46.
5. Reichard HA, Schiffer HH, Monenschein H, Atienza JM, Corbett G, Skaggs AW, Collia DR, Ray WJ, Serrats J, Bliesath J, Kaushal N, Lam BP, Amador-Arjona A, Rahbaek L, McConn DJ, Mulligan VJ, Brice N, Gaskin PL, Cilia J, Hitchcock S . 6 . Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia . Journal of Medicinal Chemistry . 64 . 15 . 11527–11542 . August 2021 . 34260228 . 10.1021/acs.jmedchem.1c00820 . 235908256 .