[CAS NO. 1802326-66-4] JNJ-63533054
PRODUCTS SPECIFICATIONS [1802326-66-4]
DESCRIPTION [1802326-66-4]
Overview
| MDL | MFCD29924732 |
|---|---|
| Molecular Weight | 316.78 |
| Molecular Formula | C17H17ClN2O2 |
| SMILES | O=C(NCC(N[C@H](C1=CC=CC=C1)C)=O)C2=CC=CC(Cl)=C2 |
Summary
IC50 & Target
EC50: 16 nM (Human GPR139), 63 nM (Rat GPR139) and 28 nM (Mouse GPR139) [1]
In Vitro
JNJ-63533054 specifically activates human GPR139 in the calcium mobilization (EC
50
of 16 nM) and GTPγS binding (EC
50
of 17 nM) assays. JNJ-63533054 also activates the rat and mouse GPR139 receptor with similar potency (rat EC
50
of 63 nM, mouse EC
50
of 28 nM)
[1]
.
In a saturation study for human GPR139, a single population of high-affinity binding sites for [3H] JNJ-63533054 is observed (K
d
of 10 nM). The B
max
value is 26 pmol/mg of protein. Saturation studies for the rat GPR139 and mouse GPR139 yielded K
d
values within the same range (32 nM and 23 nM, respectively; B
max
= 8.5 pmol/mg of protein and 6.2 pmol/mg of protein, respectively)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 157.84 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.1568 mL | 15.7838 mL | 31.5676 mL |
| 5 mM | 0.6314 mL | 3.1568 mL | 6.3135 mL |
| 10 mM | 0.3157 mL | 1.5784 mL | 3.1568 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (7.89 mM); Clear solution
References
- [1] Liu C, et al. GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine. Mol Pharmacol. 2015 Nov;88(5):911-25.
- [2] Dvorak CA, et al. Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor. ACS Med Chem Lett. 2015 Jul 20;6(9):1015-8.