AlmorexantOX1R/OX2R antagonist CAS# 871224-64-5 |
- MK-4305
Catalog No.:BCC1760
CAS No.:1030377-33-3
- SB-408124 Hydrochloride
Catalog No.:BCC1929
CAS No.:1431697-90-3
- SB-674042
Catalog No.:BCC1931
CAS No.:483313-22-0
- TCS 1102
Catalog No.:BCC4063
CAS No.:916141-36-1
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 871224-64-5 | SDF | Download SDF |
| PubChem ID | 23727689 | Appearance | Powder |
| Formula | C29H31F3N2O3 | M.Wt | 512.56 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | ACT 078573 | ||
| Solubility | DMSO : ≥ 46 mg/mL (89.75 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (2R)-2-[(1S)-6,7-dimethoxy-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-3,4-dihydro-1H-isoquinolin-2-yl]-N-methyl-2-phenylacetamide | ||
| SMILES | CNC(=O)C(C1=CC=CC=C1)N2CCC3=CC(=C(C=C3C2CCC4=CC=C(C=C4)C(F)(F)F)OC)OC | ||
| Standard InChIKey | DKMACHNQISHMDN-RPLLCQBOSA-N | ||
| Standard InChI | InChI=1S/C29H31F3N2O3/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35)/t24-,27+/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Almorexant(ACT078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.
IC50 value: 1.3/0.7 nM(OX1/OX2 receptor) [1] [2]
Target: Dual OX!/OX2 receptor
in vitro: [(3)H]Almorexant bound to a single saturable site on hOX(1) and hOX(2) with high affinity (K(d) of 1.3 and 0.17 nM, respectively. In Schild analyses using the [(3)H]inositol phosphates assay, almorexant acted as a competitive antagonist at hOX(1) and as a noncompetitive-like antagonist at hOX(2). In binding kinetic analyses, [(3)H]almorexant had fast association and dissociation rates at hOX(1), whereas it had a fast association rate and a remarkably slow dissociation rate at hOX(2) [1].
in vivo: During the 12-h dark period after dosing, ALM(Almorexant) exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness [3]. Almorexant 200 mg showed significantly less 'Drug Liking' than both zolpidem doses (p < 0.01), and almorexant 400 mg had smaller effects than zolpidem 20 mg (p < 0.05), while almorexant 1,000 mg was not different from either zolpidem dose [4]. References: | |||||
Almorexant Dilution Calculator
Almorexant Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.951 mL | 9.755 mL | 19.5099 mL | 39.0198 mL | 48.7748 mL |
| 5 mM | 0.3902 mL | 1.951 mL | 3.902 mL | 7.804 mL | 9.755 mL |
| 10 mM | 0.1951 mL | 0.9755 mL | 1.951 mL | 3.902 mL | 4.8775 mL |
| 50 mM | 0.039 mL | 0.1951 mL | 0.3902 mL | 0.7804 mL | 0.9755 mL |
| 100 mM | 0.0195 mL | 0.0975 mL | 0.1951 mL | 0.3902 mL | 0.4877 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Almorexant is an antagonist of Orexin 1 receptor (OX1R) and Orexin 2 receptor (OX2R) with Kd values of 1.3nM and 0.17nM, respectively [1].
Almorexant is a dual OX antagonist. It inhibits the binding of orexin-A to both OX1R and OX2R with IC50 values of 6.6nM and 3.4nM, respectively. In the inositol phosphates assay, almorexant acts as a competitive antagonist of hOX1R but a noncompetitive-like antagonist of hOX2R. Besides that, almorexant is found to block the increase in locomotor activity induced by ICV orexin in C57BL/6 mice. Furthermore, almorexant shows effects on sleep in multiple species, including man. It reduces the time spent awake and increased the time spent in NREM and REM sleep dose-dependently in normal C57BL/6 mice. These effects on sleep caused by almorexant are mediated by OX2Rs as almorexant has no effect in mice lacking both OX1R and OX2R but has effects in mice lacking only OX1R [1, 2].
References:
[1] Malherbe P, Borroni E, Pinard E, Wettstein JG, Knoflach F. 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.
[2] Mang GM1, Dürst T, Bürki H, Imobersteg S, Abramowski D, Schuepbach E, Hoyer D, Fendt M, Gee CE. The dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors. Sleep. 2012 Dec 1;35(12):1625-35.
- TCS 3035
Catalog No.:BCC8036
CAS No.:871085-49-3
- Raltegravir potassium salt
Catalog No.:BCC5457
CAS No.:871038-72-1
- TAK-285
Catalog No.:BCC3860
CAS No.:871026-44-7
- 5-Methoxystrictamine
Catalog No.:BCN4416
CAS No.:870995-64-5
- Neuromedin B (porcine)
Catalog No.:BCC5841
CAS No.:87096-84-2
- 5-Hydroxy-1,7-diphenyl-6-hepten-3-one
Catalog No.:BCN1321
CAS No.:87095-74-7
- Mulberrofuran G
Catalog No.:BCN3693
CAS No.:87085-00-5
- E 2012
Catalog No.:BCC1540
CAS No.:870843-42-8
- MK 0893
Catalog No.:BCC1752
CAS No.:870823-12-4
- Leptomycin B
Catalog No.:BCC7223
CAS No.:87081-35-4
- AC 261066
Catalog No.:BCC7848
CAS No.:870773-76-5
- PAP-1
Catalog No.:BCC1836
CAS No.:870653-45-5
- Isoneochamaejasmine A
Catalog No.:BCN3131
CAS No.:871319-96-9
- SC 66
Catalog No.:BCC6160
CAS No.:871361-88-5
- CTEP (RO4956371)
Catalog No.:BCC4599
CAS No.:871362-31-1
- H-1152 dihydrochloride
Catalog No.:BCC1616
CAS No.:871543-07-6
- Schisanlactone A
Catalog No.:BCN3185
CAS No.:87164-31-6
- Trametinib (GSK1120212)
Catalog No.:BCC1282
CAS No.:871700-17-3
- 2-Deacetoxydecinnamoyltaxinine J
Catalog No.:BCN7218
CAS No.:87193-98-4
- WAY 207024 dihydrochloride
Catalog No.:BCC7802
CAS No.:872002-73-8
- Dihydrotanshinone I
Catalog No.:BCN4417
CAS No.:87205-99-0
- K 114
Catalog No.:BCC5984
CAS No.:872201-12-2
- Dipraglurant
Catalog No.:BCC1531
CAS No.:872363-17-2
- NVP-QAV680
Catalog No.:BCC5508
CAS No.:872365-16-7
Dual Orexin Receptor Antagonist, Almorexant, in Elderly Patients With Primary Insomnia: A Randomized, Controlled Study.[Pubmed:28364509]
Sleep. 2017 Feb 1;40(2). pii: 2740595.
Objective: Sleep laboratory study to determine the dose-related efficacy and safety of Almorexant in elderly patients with primary chronic insomnia. Methods: Patients aged >/=65 years with primary insomnia were enrolled into a prospective, randomized, double-blind, placebo-controlled, multicenter dose-finding study with a five-period, five-way Latin square cross-over design. Patients were randomized to one of 10 unique sequences of two-night treatment with oral Almorexant 25, 50, 100, or 200 mg capsules, or matching placebo. The primary efficacy endpoint was polysomnography (PSG)-determined mean wake time after sleep onset (WASO). Secondary and exploratory efficacy endpoints were also assessed. Results: 112 patients were randomized (mean [SD] age 72.1 [5.0] years; 69.9% female). Significant, dose-related improvements (reductions) in mean WASO were observed with Almorexant. Least-squares mean (95% CI) treatment effects in the Almorexant 200, 100, 50, and 25 mg dose groups versus placebo were -46.5 minutes (-53.0, -39.9; p < .0001), -31.4 minutes (-38.0, -24.9; p < .0001), -19.2 minutes (-25.7, -12.6; p < .0001), and -10.4 minutes (-17.0, -3.9; p = .0018), respectively. Mean total sleep time was significantly increased with each Almorexant dose (mean increases versus placebo ranged 55.1-14.3 minutes; p < .0001 for each dose). Latency to persistent sleep was statistically significantly reduced only with Almorexant 200 mg versus placebo (mean [95% CI] treatment effect -10.2 minutes, [-15.4, -5.0]; p = .0001). No unexpected safety concerns were identified. Adverse events were similar between all Almorexant dose groups and placebo. Conclusions: Two-night oral administration of Almorexant was effective and well tolerated in treating primary insomnia in elderly patients.
The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems.[Pubmed:26289145]
Neuropsychopharmacology. 2016 Mar;41(4):1144-55.
The dual hypocretin receptor (HcrtR) antagonist Almorexant (ALM) may promote sleep through selective disfacilitation of wake-promoting systems, whereas benzodiazepine receptor agonists (BzRAs) such as zolpidem (ZOL) induce sleep through general inhibition of neural activity. Previous studies have indicated that HcrtR antagonists cause less-functional impairment than BzRAs. To gain insight into the mechanisms underlying these differential profiles, we compared the effects of ALM and ZOL on functional activation of wake-promoting systems at doses equipotent for sleep induction. Sprague-Dawley rats, implanted for EEG/EMG recording, were orally administered vehicle (VEH), 100 mg/kg ALM, or 100 mg/kg ZOL during their active phase and either left undisturbed or kept awake for 90 min after which their brains were collected. ZOL-treated rats required more stimulation to maintain wakefulness than VEH- or ALM-treated rats. We measured Fos co-expression with markers for wake-promoting cell groups in the lateral hypothalamus (Hcrt), tuberomammillary nuclei (histamine; HA), basal forebrain (acetylcholine; ACh), dorsal raphe (serotonin; 5HT), and singly labeled Fos(+) cells in the locus coeruleus (LC). Following SD, Fos co-expression in Hcrt, HA, and ACh neurons (but not in 5HT neurons) was consistently elevated in VEH- and ALM-treated rats, whereas Fos expression in these neuronal groups was unaffected by SD in ZOL-treated rats. Surprisingly, Fos expression in the LC was elevated in ZOL- but not in VEH- or ALM-treated SD animals. These results indicate that Hcrt signaling is unnecessary for the activation of Hcrt, HA, or ACh wake-active neurons, which may underlie the milder cognitive impairment produced by HcrtR antagonists compared to ZOL.
Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine.[Pubmed:24880753]
Eur Neuropsychopharmacol. 2014 Aug;24(8):1257-68.
Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling effects in humans. Insomnia is often associated with mental health problems, including depression. Hence, potential interactions with antidepressants deserve attention. Desipramine was selected as a model drug because it is mainly metabolized by CYP2D6, which is inhibited by Almorexant in vitro. A single-center, randomized, placebo-controlled, two-way crossover study in 20 healthy male subjects was conducted to evaluate the pharmacokinetic and pharmacodynamic interactions between Almorexant and desipramine. Almorexant 200mg or matching placebo (double-blind) was administered orally once daily in the morning for 10 days, and a single oral dose of 50mg desipramine (open-label) was administered on Day 5. Almorexant increased the exposure to desipramine 3.7-fold, suggesting that Almorexant is a moderate inhibitor of desipramine metabolism through inhibition of CYP2D6. Conversely, desipramine showed no relevant effects on the pharmacokinetics of Almorexant. Pharmacodynamic evaluations indicated that Almorexant alone reduced visuomotor coordination, postural stability, and alertness, and slightly increased calmness. Desipramine induced a reduction in subjective alertness and an increase in pupil/iris ratio. Despite the increase in exposure to desipramine, Almorexant and desipramine in combination showed the same pharmacodynamic profile as Almorexant alone, except for prolonging reduced alertness and preventing the miotic effect of Almorexant. Co-administration also prolonged the mydriatic effect of desipramine. Overall, repeated administration of Almorexant alone or with single-dose desipramine was well tolerated. The lack of a relevant interaction with antidepressants, if confirmed for other DORAs, would be a key feature for a safer class of hypnotics.
