TAK-994

TAK-994 is an orexin receptor 2 (OX2R) agonist.^1,2 It selectively induces calcium mobilization in CHO-K1 cells expressing human OX2R over those expressing OX1R (EC₅₀s = 0.019 and 14 µM, respectively).¹ TAK-994 is also selective for OX2R over a panel of 106 enzymes, receptors, and ion channels at 10 µM. In vivo, TAK-994 (3 mg/kg) increases wakefulness time and wakefulness episode duration and inhibits chocolate-induced cataplexy-like episodes during the active phase in a model of narcolepsy using mice with orexin neurons ablated by ataxin-3 expression. It increases wakefulness time but does not affect orexin A (OXA) or OXB cerebrospinal fluid (CSF) levels during the sleep phase in cynomolgus monkeys when administered at a dose of 10 mg/kg.²

WARNING This product is not for human or veterinary use.

1. Ishikawa, T., Hara, H., Kawano, A., et al. TAK-994, a novel orally available brain-penetrant orexin 2 receptor-selective agonist, suppresses fragmentation of wakefulness and cataplexy-like episodes in mouse models of narcolepsy. J. Pharmacol. Exp. Ther. 385(3), 193-204 (2023).

2. Yamada, R., Narita, N., Ishikawa, T., et al. The orexin receptor 2 (OX2R)-selective agonist TAK-994 increases wakefulness without affecting cerebrospinal fluid orexin levels in cynomolgus monkeys. Pharmacol. Biochem. Behav. 234, 173690 (2024).