| CAS |
No.1373765-19-5 |
| 英文名称 |
IPSU |
| 分子式 |
C23H27N5O2 |
| 分子量 |
405.49 |
| 溶解性 |
Soluble in DMSO ≥3mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| 靶点 |
Orexin Receptor (OX Receptor) |
| 通路 |
GPCR & G Protein;Neuronal Signaling |
| 背景说明 |
IPSU是一种选择性，有口服活性和脑渗透性的OX2R拮抗剂。 |
| 生物活性 |
IPSU is a selective， orally available and brain penetrant OX2R antagonist with a pKi of 7.85.[1-3] |
| IC50 |
pKi: 7.85 (OX2R)， 6.29 (OX1R)[1] |
| In Vitro |
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]. |
| 动物实验 |
Mice: Freely moving C57Bl/6 mice with chronically implanted electrodes are well abituated to the experiment boxes and had access to food and ater ad libitum. The test compounds (IPSU) or vehicle are administered per os as a suspension in 0.5% methylcellulose immediately prior to lights off and start of recording. Movement is recorded using infrared sensors in the roof of the box. EEG/EMG signals and motility data are used to score 10 s epochs into wake， NREM sleep， and REM sleep. Each animal served as its own control by application and recording of vehicle the day before compound (IPSU) dosing[1]. |
| 激酶实验 |
Competition experiments are performed with a single concentration of radioligand and six concentrations of competitor (unlabeled ligands; BBAC， almorexant， SB-649868， suvorexant， filorexant or IPSU). 4.6 nM [3H]-BBAC is added simultaneously with various concentrations of unlabeled ligand (0.1 nM-10 μM) to membranes (150 μL/well) in 50 μL/well of assay buffer with a total volume of 250 μL/well. The amount of [3H]-BBAC bound to receptors is determined at room temperature at different time points (ranging from 15 min to 4 h) and terminated by rapid vacuum filtration and liquid scintillation counting[2]. |
| 数据来源文献 |
[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. |
| 规格 |
1mg 5mg 10mg 25mg |
| 单位 |
瓶 |
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