Almorexant (ACT 078573) 是一种口服有效且竞争性的双orexin receptor拮抗剂，Kd分别为 1.3 nM (OX1) 和 0.17 nM (OX2)。Almorexant 可逆地阻断食欲素-A 和食欲素-B 多肽信号。Almorexant 完全阻断细胞内Ca2+信号通路。Almorexant 刺激 AsPC-1 细胞caspase-3活性，诱导细胞凋亡 (apoptosis)。
| 生物活性 | Almorexant (ACT 078573) is an orally active, potent and competitive dualorexin receptorantagonist, withKdvalues of 1.3 nM (OX1) and 0.17 nM (OX2), respectively. Almorexant reversibly blocks signaling of orexin-A and orexin-Bpeptides. Almorexant totally blocked the intracellularCa2+signal pathway. Almorexant stimulatescaspase-3activity in AsPC-1 cells and inducesapoptosis[1][2][3][4]. |
| IC50& Target | human OX2R 0.17 nM (Kd) | human OX1R 1.3 nM (Kd) | Caspase-3 |
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体外研究
(In Vitro) | Almorexant (1 μM) promotes tyrosine phosphorylation of SHP2/OX1R complex[1].
Almorexant (1 μM) inhibits the cellular growth of AsPC-1 cells[1].
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体内研究
(In Vivo) | Almorexant (1.8 μmol/kg, 100 μL; IP, daily) reduces the volume of tumors[2].
Almorexant (300 mg/kg, PO, once) can help rats to be fully capable of spatial and avoidance learning[4].
Almorexant (30-300 mg/kg) dose-dependently increases rapid eye movement (REM) and non-REM (NREM) sleep and decreases wakefulness apparently without inducing either cataplexy18 or deficits in next-day performance[3].
| Animal Model: | Mice xenografted with AsPC-1 cells[2] | | Dosage: | 1.8 μmol/kg, 100 μL | | Administration: | IP, daily, starting at day 0 or day 38 | | Result: | Resulted in a significant decrease in tumor volume when treatment starting at day 0. Started after AsPC-1 tumors were developed (day 38), rapidly and strongly reduced the volume of established tumors. |
| Animal Model: | Long-Evans rats (24, male, 16-18 weeks of age)[4] | | Dosage: | 300 mg/kg | | Administration: | PO, once | | Result: | Successfully learned the spatial task, established spatial memory. |
| Animal Model: | Male C57BL/6 mice (Orexin/ataxin-3transgenic (TG) mice and WT mice, 32 ± 0.9 g, age 15 ± 0.5 week)[3] | | Dosage: | 30, 100, 300 mg/kg (3, 10, and 30 mg/mL; 10 mL/kg) | | Administration: | IP, once every 3 days | | Result: | Exacerbated cataplexy in TG mice and increased nonrapid eye movement (NREM) sleep with heightened sleep/wake fragmentation in both genotypes during the 12-h dark period after dosing. Showed greater hypnotic potency in WT mice than in TG mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 46 mg/mL(89.75 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.9510 mL | 9.7550 mL | 19.5099 mL | | 5 mM | 0.3902 mL | 1.9510 mL | 3.9020 mL | | 10 mM | 0.1951 mL | 0.9755 mL | 1.9510 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (4.88 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.88 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.88 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.88 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (4.88 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.88 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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