JNJ-42153605 is a potent, selective and allosteric modulator of the mGlu2 (metabotropic glutamate 2) receptor with with an EC50 of 17 nM. IT has an excellent pharmacokinetic profile in rodent and nonrodent species. JNJ-42153605 is assessed for its selectivity for the mGlu2 receptor and is found to not have agonist or antagonist activity toward other mGlu receptor subtypes up to 30 μM. JNJ-42153605 shows high permeability with no indication for P-glycoprotein efflux. JNJ-42153605 showed a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown earlier to be mGlu2 mediated. In mice, JNJ-42153605 reversed PCP-induced hyperlocomotion with an ED50 of 5.4 mg/kg sc, indicative of antipsychotic activity.
理化性质和储存条件
| Molecular Weight (MW) | 400.44 |
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| Formula | C22H23F3N4 |
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| CAS No. | 1254977-87-1 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 10 mM |
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| Water: <1 mg/mL |
| Ethanol: |
| SMILES Code | FC(C1=C(N2CCC(C3=CC=CC=C3)CC2)C=CN4C1=NN=C4CC5CC5)(F)F |
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| Synonyms | JNJ-42153605; JNJ 42153605; JNJ42153605 |
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实验参考方法
| In Vitro | In vitro activity: JNJ-42153605 is a potent, selective and allosteric modulator of the mGlu2 (metabotropic glutamate 2) receptor with with an EC50 of 17 nM. IT has an excellent pharmacokinetic profile in rodent and nonrodent species. JNJ-42153605 is assessed for its selectivity for the mGlu2 receptor and is found to not have agonist or antagonist activity toward other mGlu receptor subtypes up to 30 μM. JNJ-42153605 shows high permeability with no indication for P-glycoprotein efflux. JNJ-42153605 showed a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown earlier to be mGlu2 mediated. In mice, JNJ-42153605 reversed PCP-induced hyperlocomotion with an ED50 of 5.4 mg/kg sc, indicative of antipsychotic activity.
Kinase Assay: JNJ-42153605 is a potent, selective and allosteric modulator of the mGlu2 (metabotropic glutamate 2) receptor with with an EC50 of 17 nM. JNJ-42153605 is assessed for its selectivity for the mGlu2 receptor and is found to not have agonist or antagonist activity toward other mGlu receptor subtypes up to 30 μM. JNJ-42153605 shows high permeability with no indication for P-glycoprotein efflux
Cell Assay: |
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| In Vivo | JNJ-42153605 shows a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown to be mGlu2 mediated. In mice, JNJ-42153605 shows reversed PCP-induced hyperlocomotion with an ED50 of 5.4 mg/kg sc, indicative of antipsychotic activity. JNJ-42153605 shows a rapid rate of absorption from the gastrointestinal tract, reaching the maximal concentration after 0.5 h. Clearance in vivo is moderate to high in both rat and dog (35 and 29 mL/min/kg, respectively). Elimination halflives are on the shorter side across the species, being 2.7 h in rat and 0.8-1.1 h in dog |
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| Animal model | Mice |
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| Formulation & Dosage | 5.4 mg/kg sc |
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| References | J Med Chem. 2012 Oct 25;55(20):8770-89. |
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