[CAS NO. 913358-93-7] Almorexant hydrochloride
PRODUCTS SPECIFICATIONS [913358-93-7]
DESCRIPTION [913358-93-7]
Overview
| MDL | MFCD14636620 |
|---|---|
| Molecular Weight | 549.02 |
| Molecular Formula | C29H32ClF3N2O3 |
| SMILES | CNC([C@@H](C1=CC=CC=C1)N2CCC3=CC(OC)=C(OC)C=C3[C@@H]2CCC4=CC=C(C(F)(F)F)C=C4)=O.Cl |
2 Publications Citing Use of MCE
Summary
Almorexant (ACT 078573) hydrochloride is an orally active, potent and competitive dual orexin receptor antagonist, with K d values of 1.3 nM ( OX1 ) and 0.17 nM ( OX2 ), respectively. Almorexant hydrochloride reversibly blocks signaling of orexin-A and orexin-B peptides . Almorexant hydrochloride totally blocked the intracellular Ca 2+ signal pathway. Almorexant hydrochloride stimulates caspase-3 activity in AsPC-1 cells and induces apoptosis [1] [2] [3] [4] .
IC50 & Target
|
human OX2R 0.17 nM (Kd) |
human OX1R 1.3 nM (Kd) |
Caspase-3
|
In Vitro
In Vivo
Almorexant hydrochloride (1.8 μmol/kg, 100 μL; IP, daily) reduces the volume of tumors
[2]
.
Almorexant hydrochloride (300 mg/kg, PO, once) can help rats to be fully capable of spatial and avoidance learning
[4]
.
Almorexant hydrochloride (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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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-3 transgenic (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. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00608985 | Midnight Pharma, LLC |
Primary Insomnia
|
March 2008 | Phase 3 |
| NCT00606593 | Midnight Pharma, LLC |
Chronic Primary Insomnia
|
December 2007 | Phase 2 |
| NCT01987739 | Midnight Pharma, LLC |
Abuse Potential Study
|
September 2009 | Phase 1 |
| NCT00640848 | Midnight Pharma, LLC |
Insomnia|Primary Insomnia
|
May 2006 | Phase 1 |
| NCT01954589 | Idorsia Pharmaceuticals Ltd. |
Safety|Tolerability|Pharmacodynamics|Pharmacokinetics
|
November 2011 | Phase 1 |
| NCT01243060 | Northern California Institute of Research and Education|U.S. Army Medical Research and Development Command |
Healthy Volunteers
|
May 2011 | Not Applicable |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : ≥ 46 mg/mL ( 83.79 mM )
H 2 O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8214 mL | 9.1071 mL | 18.2143 mL |
| 5 mM | 0.3643 mL | 1.8214 mL | 3.6429 mL |
| 10 mM | 0.1821 mL | 0.9107 mL | 1.8214 mL |
References
- [1] Dayot S, et al. In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin-1/orexin-A and almorexant in pancreatic ductal adenocarcinoma. Oncotarget. 2018 Jan 9;9(6):6952-6967.
- [2] Malherbe P, et al. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31.
- [3] Black SW, et al. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013 Mar 1;36(3):325-36.
- [4] Dietrich H, et al. Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant. Psychopharmacology (Berl). 2010 Oct;212(2):145-54.