molecules of the month

JNJ-54717793 is a selective antagonist of the orexin-1 receptor intended for use in anxiety disorders, in contrast to dual orexin-1/2 inhibitors and orexin-2 inhibitors typically applied for sleep disorders. It’s a surprisingly large molecule (three aromatic rings and a bicycle) for an oral, brain-penetrant clinical candidate with predicted once-daily dosing in humans. This compound was very well-tolerated in preclinical species (NOAEL 250 mg/kg in rodent, 25 mg/kg in dog).