Uses
JNJ-54717793, as a brain penetrant, is an orally active, selective and high affinity orexin-1 receptor (OX1R) antagonist (plasma EC50=85 ng/mL). The Ki values of JNJ-54717793 for hOX1R (human OX1R) and hOX2R are 16 nM and 700 nM, respectively. JNJ-54717793 is a potent compound of anxiety disorders[1][2].
Biological Activity
JNJ-54717793, as a brain penetrant, is an orally active, selective and high affinity orexin-1 receptor (OX1R) antagonist (plasma EC50=85 ng/mL). The Ki values of JNJ-54717793 for hOX1R (human OX1R) and hOX2R are 16 nM and 700 nM, respectively. JNJ-54717793 is a potent compound of anxiety disorders[1][2].
JNJ-5471779 (30 mg/kg; p.o.; 6 hours) significantly reduces the latency for rapid eye movement (REM) sleep and prolongs the time spent in REM sleep[2].JNJ-5471779 (3~30 mg/kg; p.o.) attenuates bradycardia responses[2].JNJ-5471779 (5mg/kg; p.o.) shows low clearance[1].
in vivo
JNJ-5471779 (30 mg/kg; p.o.; 6 hours) significantly reduces the latency for rapid eye movement (REM) sleep and prolongs the time spent in REM sleep[2].
JNJ-5471779 (3~30 mg/kg; p.o.) attenuates bradycardia responses[2].
JNJ-5471779 (5mg/kg; p.o.) shows low clearance[1].
| Animal Model: | OX2R KO mice[2] |
| Dosage: | 30 mg/kg |
| Administration: | P.o. |
| Result: | Significantly reduced the latency for rapid eye movement (REM) sleep and prolonged the time spent in REM sleep. |
| Animal Model: | Rat[2] |
| Dosage: | 3~30 mg/kg |
| Administration: | P.o. |
| Result: | Attenuated bradycardia responses. |
| Animal Model: | Mouse[1] |
| Dosage: | 5.0 mg/kg (Pharmacokinetic Analysis) |
| Administration: | P.o. |
| Result: | Clearance was found to be low. |
IC 50
human OX1R: 16 nM (Ki); human OX2R: 700 nM (Ki); OX1 Receptor: 85 ng/mL (EC50)
References
[1]. Préville C, et al. Substituted Azabicyclo[2.2.1]heptanes as Selective Orexin-1 Antagonists: Discovery of JNJ-54717793. ACS Med Chem Lett. 2020;11(10):2002-2009. Published 2020 Apr 27. [2]. Bonaventure P, et al. Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation. Front Pharmacol. 2017;8:357. Published 2017 Jun 9.
