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G-protein coupled receptor 139 (GPC139) is a protein that in humans is encoded by the GPR139gene.[5][6] 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.[7][8]
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Ligands
Agonists
Zelatriazin (TAK-41), (NBI-1065846) a potent, and GPR139 receptor selective agonist [9] 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.
^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. doi:10.1111/bcpt.13263PMID31132229
^Reichard HA, Schiffer HH, Monenschein H, Atienza JM, Corbett G, Skaggs AW, et al. (August 2021). "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. doi:10.1021/acs.jmedchem.1c00820. PMID34260228. S2CID235908256.
Further reading
Vanti WB, Nguyen T, Cheng R, Lynch KR, George SR, O'Dowd BF (May 2003). "Novel human G-protein-coupled receptors". Biochemical and Biophysical Research Communications. 305 (1): 67–71. doi:10.1016/S0006-291X(03)00709-5. PMID12732197.
Ottolenghi C, Fellous M, Barbieri M, McElreavey K (March 2002). "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. doi:10.1006/geno.2002.6711. PMID11863363.
Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters. 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID12044878. S2CID7116392.
Gloriam DE, Schiöth HB, Fredriksson R (April 2005). "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. doi:10.1016/j.bbagen.2004.12.001. PMID15777626.
Matsuo A, Matsumoto S, Nagano M, Masumoto KH, Takasaki J, Matsumoto M, et al. (May 2005). "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. doi:10.1016/j.bbrc.2005.03.174. PMID15845401.