JNJ-54717793

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].

Signaling Pathways >> GPCR/G Protein >> Orexin Receptor (OX Receptor)

Research Areas >> Neurological Disease

human OX1R:16 nM (Ki)

human OX2R:700 nM (Ki)

OX1 Receptor:85 ng/mL (EC50)

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.

[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.