Oveporexton (TAK-861) is an orally active and selective orexin receptor 2 (OX2R) agonist with an EC 50 of 2.5 nM. Oveporexton exhibits 3000-fold selectivity for OX2R over OX1R. Oveporexton can be used for the study of hypersomnia disorders including narcolepsy [1] [2].
In Vivo, Oveporexton (0.03-10 mg/kg; p.o.) improves narcolepsy-like phenotype in mice, significantly increasing total waking time[2]. Oveporexton (1 mg/kg; p.o.) significantly increases wakefulness time in cynomolgus monkeys[2].
In Vitro, Oveporexton potently activates recombinant OX2R (EC50 of 2.5 nM) and weakly activates OX1R (EC50 of 7500 nM)[2]. Oveporexton (10-1000 nM) induces dose-dependent depolarization of the membrane potential in histaminergic neurons in the mouse tuberomammillary nucleus with an EC50 of 31.7 nM[2].
References:
[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 38, No. 2, 2024.
[2]. Mitsukawa K, et al. TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models. Sci Rep. 2024 Sep 6;14(1):20838.
In Vivo, Oveporexton (0.03-10 mg/kg; p.o.) improves narcolepsy-like phenotype in mice, significantly increasing total waking time[2]. Oveporexton (1 mg/kg; p.o.) significantly increases wakefulness time in cynomolgus monkeys[2].
In Vitro, Oveporexton potently activates recombinant OX2R (EC50 of 2.5 nM) and weakly activates OX1R (EC50 of 7500 nM)[2]. Oveporexton (10-1000 nM) induces dose-dependent depolarization of the membrane potential in histaminergic neurons in the mouse tuberomammillary nucleus with an EC50 of 31.7 nM[2].
References:
[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 38, No. 2, 2024.
[2]. Mitsukawa K, et al. TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models. Sci Rep. 2024 Sep 6;14(1):20838.