ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors JNJ 63533054

JNJ 63533054

Product NameJNJ 63533054
CAS1802326-66-4
MFC17H17ClN2O2
MW316.78
EINECS
MOL File1802326-66-4.mol

Chemical Properties

Boiling point	559.7±45.0 °C(Predicted)
Density	1.224±0.06 g/cm3(Predicted)
storage temp.	room temp
solubility	Soluble in DMSO (up to 35 mg/ml).
pka	12.77±0.46(Predicted)
form	powder
color	white to beige
optical activity	[α]/D -89 to -99°, c = 1 in ethanol
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
InChIKey	MWDVCHRYCKXEBY-LBPRGKRZSA-N
SMILES	Clc1cc(ccc1)C(=O)NCC(=O)N[C@@H](C)c2ccccc2

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids
Hazard Classifications	Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2

Usage And Synthesis

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

Uses

JNJ 63533054 is a potent and selective agonist of hGPR139 with an EC50 = 16 nM.

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.

in vivo

JNJ-63533054 (3-30 mg/kg; oral administration; once; SD rats) treatment induces a dose-dependent reduction in locomotor activity in the first hour^[1].
The pharmacokinetics of JNJ-63533054 (Compound 7c; 1 mg/kg iv; 5 mg/kg po) in rat is examined. The IV clearance is 53 mL/min/kg, the C_max is 317 ng/mL (~1 μM), the t_1/2 is 2.5 hours, and JNJ-63533054 is able to cross the blood-brain barrier (BBB) with a brain to plasma ratio (b/p) of 1.2^[2].

Animal Model:	Male Sprague-Dawley rats (350-450 g)^[1]
Dosage:	3 mg/kg, 10 mg/kg, and 30 mg/kg
Administration:	Oral administration; once
Result:	Induced a dose-dependent reduction in locomotor activity in the first hour.

storage

Store at RT

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

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