JNJ-63533054

JNJ-63533054
Identifiers
	IUPAC name 3-chloro-N-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzamide;
CAS Number	1802326-66-4;
PubChem CID	2548547;
IUPHAR/BPS	8766;
ChemSpider	1896806;
ChEMBL	ChEMBL3633720;
PDB ligand	7ZQ (PDBe, RCSB PDB);
Chemical and physical data
Formula	C17H17ClN2O2
Molar mass	316.79 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H](C1=CC=CC=C1)NC(=O)CNC(=O)C2=CC(=CC=C2)Cl;
	InChI InChI=1S/C17H17ClN2O2/c1-12(13-6-3-2-4-7-13)20-16(21)11-19-17(22)14-8-5-9-15(18)10-14/h2-10,12H,11H2,1H3,(H,19,22)(H,20,21)/t12-/m0/s1; Key:MWDVCHRYCKXEBY-LBPRGKRZSA-N;

JNJ-63533054 is a chemical compound which acts as a small-molecule agonist of the previously orphan receptor GPR139.^[1]^[2]^[3] It has been used to investigate the role of GPR139 in various behavioral processes^[4] including sleep,^[5] anxiety,^[6] addiction,^[7] and cognition.^[8]

References

^ Dvorak CA, Coate H, Nepomuceno D, Wennerholm M, Kuei C, Lord B, et al. (September 2015). "Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor". ACS Medicinal Chemistry Letters. 6 (9): 1015–1018. doi:10.1021/acsmedchemlett.5b00247. PMC 4569879. PMID 26396690.
^ Liu C, Bonaventure P, Lee G, Nepomuceno D, Kuei C, Wu J, et al. (November 2015). "GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine". Molecular Pharmacology. 88 (5): 911–925. doi:10.1124/mol.115.100412. PMID 26349500.
^ Pallareti L, Rath TF, Trapkov B, Tsonkov T, Nielsen AT, Harpsøe K, et al. (March 2023). "Pharmacological characterization of novel small molecule agonists and antagonists for the orphan receptor GPR139". European Journal of Pharmacology. 943 175553. doi:10.1016/j.ejphar.2023.175553. PMID 36736525.
^ Chan M, Ogawa S (July 2025). "GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders". Molecular Neurobiology. 62 (7): 9324–9337. doi:10.1007/s12035-025-04828-2. PMC 12208981. PMID 40102345.
^ Wang L, Dugovic C, Yun S, White A, Lord B, Dvorak C, et al. (September 2020). "Putative role of GPR139 on sleep modulation using pharmacological and genetic rodent models". European Journal of Pharmacology. 882 173256. doi:10.1016/j.ejphar.2020.173256. PMID 32531213.
^ Roy N, Ogawa S, Tsuda S, Parhar IS (2024). "GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish". Frontiers in Neuroscience. 18 1461148. doi:10.3389/fnins.2024.1461148. PMC 11665214. PMID 39717703.
^ Kononoff J, Kallupi M, Kimbrough A, Conlisk D, de Guglielmo G, George O (2018). "Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats". eNeuro. 5 (3). doi:10.1523/ENEURO.0153-18.2018. PMC 6027959. PMID 29971251.
^ Mu R, Hou X, Liu Q, Wang W, Qin C, Li H (March 2024). "Up-regulation of GPR139 in the medial septum ameliorates cognitive impairment in two mouse models of Alzheimer's disease". International Immunopharmacology. 130 111786. doi:10.1016/j.intimp.2024.111786. PMID 38447415.

[Dvorak_2015-1] Dvorak CA, Coate H, Nepomuceno D, Wennerholm M, Kuei C, Lord B, et al. (September 2015). "Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor". ACS Medicinal Chemistry Letters. 6 (9): 1015–1018. doi:10.1021/acsmedchemlett.5b00247. PMC 4569879. PMID 26396690.

[Liu_2015-2] Liu C, Bonaventure P, Lee G, Nepomuceno D, Kuei C, Wu J, et al. (November 2015). "GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine". Molecular Pharmacology. 88 (5): 911–925. doi:10.1124/mol.115.100412. PMID 26349500.

[Pallareti_2023-3] Pallareti L, Rath TF, Trapkov B, Tsonkov T, Nielsen AT, Harpsøe K, et al. (March 2023). "Pharmacological characterization of novel small molecule agonists and antagonists for the orphan receptor GPR139". European Journal of Pharmacology. 943 175553. doi:10.1016/j.ejphar.2023.175553. PMID 36736525.

[Chan_2025-4] Chan M, Ogawa S (July 2025). "GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders". Molecular Neurobiology. 62 (7): 9324–9337. doi:10.1007/s12035-025-04828-2. PMC 12208981. PMID 40102345.

[Wang_2020-5] Wang L, Dugovic C, Yun S, White A, Lord B, Dvorak C, et al. (September 2020). "Putative role of GPR139 on sleep modulation using pharmacological and genetic rodent models". European Journal of Pharmacology. 882 173256. doi:10.1016/j.ejphar.2020.173256. PMID 32531213.

[Roy_2024-6] Roy N, Ogawa S, Tsuda S, Parhar IS (2024). "GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish". Frontiers in Neuroscience. 18 1461148. doi:10.3389/fnins.2024.1461148. PMC 11665214. PMID 39717703.

[Kononoff_2018-7] Kononoff J, Kallupi M, Kimbrough A, Conlisk D, de Guglielmo G, George O (2018). "Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats". eNeuro. 5 (3). doi:10.1523/ENEURO.0153-18.2018. PMC 6027959. PMID 29971251.

[Mu_2024-8] Mu R, Hou X, Liu Q, Wang W, Qin C, Li H (March 2024). "Up-regulation of GPR139 in the medial septum ameliorates cognitive impairment in two mouse models of Alzheimer's disease". International Immunopharmacology. 130 111786. doi:10.1016/j.intimp.2024.111786. PMID 38447415.

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