| Bioactivity | IPSU is a selective, orally available and brain penetrant OX2R antagonist with a pKi of 7.85. | ||||||||||||
| Target | pKi: 7.85 (OX2R), 6.29 (OX1R) | ||||||||||||
| Invitro | Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. IPSU binds rapidly and reaches equilibrium very quickly in binding and/or functional assays[2]. | ||||||||||||
| In Vivo | IPSU has low blood clearance, shows high maximal blood exposure and AUC after oral dosing. It exhibits an acceptable absolute oral bioavailability and a brain/blood concentration ratio that indicated favorable brain penetration. IPSU increases sleep when dosed during the mouse active phase (lights off); IPSU induces sleep primarily by increasing NREM sleep. IPSU shows a fast onset of action, with a clear increase in total sleep time during the first hour afterdosing. The effect lasts 4-5 h, after which time the total sleep time per hour is the same as on vehicle day [1]. | ||||||||||||
| Name | IPSU | ||||||||||||
| CAS | 1373765-19-5 | ||||||||||||
| Formula | C23H27N5O2 | ||||||||||||
| Molar Mass | 405.49 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Betschart C, et al. Identification of a novel series of orexin receptor antagonists with a distinct effect on sleeparchitecture for the treatment of insomnia. J Med Chem. 2013 Oct 10;56(19):7590-607. [2]. Callander GE, et al. Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors. Front Neurosci. 2013 Dec 3;7:230. [3]. Hoyer D, et al. Distinct effects of IPSU and suvorexant on mouse sleep architecture. |