| Size | Price | Stock | Qty |
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| 5mg |
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Purity: ≥98%
Lu AE58054 hydrochloride (also known as Idalopirdine hydrochloride) is potent and selective antagonist of the 5-HT(6) receptor with Ki value of 0.83 nM. Lu AE58054 exhibited strong suppression of 5-HT-mediated activation but no agonist activity in a 5-HT(6) GTPgammaS efficacy assay. Lu AE58054 showed >50-fold selectivity for more than 70 targets studied in addition to medium affinity to adrenergic alpha(1A)- and alpha(1B)-adrenoreceptors. Lu AE58054 is being tested as an augmentation therapy in phase III clinical trials to treat cognitive deficits linked to schizophrenia and Alzheimer's disease.
| Targets |
5-HT6 Receptor ( Ki = 0.83 nM )
5-HT6 receptor [2] |
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| ln Vitro |
In vitro activity: In vivo binding of the 5-HT(6) antagonist radioligand [(3)H]Lu AE60157 was potently inhibited by oral administration of Lu AE58054, with an ED(50) of 2.7 mg/kg. The plasma EC(50) value of 20 ng/ml was found through steady-state modeling of an acute pharmacokinetic/5-HT(6)R occupancy time-course experiment. |
| ln Vivo |
Idalopirdine (5 mg/kg intraperitoneally injected daily for 28 days) In overeating rat models, hydrochloride can lower body weight and food intake[1].
Idalopirdine (i.v., 1 or 2 mg/kg) While donepezil's effect on cortical gamma oscillations can be enhanced by hydrochloride in a dose-dependent manner during nPO electrical stimulation, rats' sleep-wake patterns remain unchanged[2]. 1. In a rat model of excessive eating, Lu AE58054 hydrochloride (administered intraperitoneally at 5 mg/kg body weight per day for 28 consecutive days) significantly reduced caloric intake, prevented obesity development, decreased peritoneal adipose tissue mass, and lowered plasma levels of glucose, triglycerides and total cholesterol compared with the vehicle-treated control group. Additionally, it suppressed rebound hyperphagia after a 20 h food deprivation period, and the anorectic effect was not caused by gastrointestinal abnormalities (e.g., nausea) as confirmed by pica behavior assessment [1] 2. In anesthetized Sprague-Dawley rats, Lu AE58054 hydrochloride (2 mg/kg intravenously) increased gamma power in the medial prefrontal cortex (mPFC) during electrical stimulation of the brainstem nucleus pontis oralis (nPO). In awake, freely moving rats, Lu AE58054 hydrochloride (10 mg/kg orally) potentiated the gamma power-increasing effect of donepezil (1 mg/kg subcutaneously) in the frontal cortex, without affecting sleep-wake architecture (donepezil dose-dependently delayed sleep onset and reduced REM/non-REM sleep time, while Lu AE58054 hydrochloride did not alter sleep-wake patterns nor interfere with donepezil's effects on sleep) [2] |
| Animal Protocol |
Male Wistar rats
5 mg/kg intraperitoneal injection, daily, 28 days 1. Experiment 1 (excessive eating model in male Wistar rats): Lu AE58054 hydrochloride was dissolved in 5% 2-hydroxypropyl-beta-cyclodextrin (vehicle). The rats were fed a high-calorie diet (consisting of milk chocolate with nuts, cheese, salted peanuts, condensed milk) with ad libitum access to standard feed and water throughout the 4-week experiment. Lu AE58054 hydrochloride was administered intraperitoneally at a dose of 5 mg/kg body weight once daily for 28 consecutive days; the control group received the vehicle only. To assess the effect on rebound hyperphagia, the drug was administered after a 20 h food deprivation period. To confirm the anorectic effect was not due to visceral illness, pica behavior was evaluated post-drug administration. After the 4-week treatment, rats were euthanized (with heparin 1000 IU/rat and thiopental 70 mg/kg body weight), peritoneal adipose tissue was collected and weighed, and plasma levels of glucose, triglycerides and total cholesterol were measured. Statistical analysis was performed using one-way ANOVA post-hoc Tukey Multiple Comparison Test or two-way ANOVA post-hoc Bonferroni Multiple Comparison Test [1] 2. Experiment 2 (cortical gamma oscillations and sleep-wake architecture in rats): For anesthetized rats (Sprague-Dawley, male), Lu AE58054 hydrochloride was administered intravenously at 2 mg/kg, and donepezil was given intravenously at 0.3/1 mg/kg; cortical gamma power in the mPFC was measured during electrical stimulation of the brainstem nPO. For awake, freely moving rats, Lu AE58054 hydrochloride was administered orally at 10 mg/kg (pretreatment), followed by donepezil at 1/3 mg/kg subcutaneously; frontal cortical gamma power was measured via electroencephalogram (EEG). Telemetric polysomnography was used to assess sleep-wake architecture (sleep onset time, time spent in REM/non-REM sleep) after administration of Lu AE58054 hydrochloride (10 mg/kg p.o.) alone or in combination with donepezil (1/3 mg/kg s.c.) [2] |
| References |
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| Additional Infomation |
1. Lu AE58054 hydrochloride (edalopyridine) is a clinically tested selective 5-HT6 receptor antagonist. Obesity is a common social problem, mainly caused by excessive intake of sweet, salty and high-fat foods; blocking 5-HT6 receptors is thought to reduce food intake, so Lu AE58054 hydrochloride has been studied as a potential anti-obesity drug. Results showed that it can reduce calorie intake and could be considered as a potential treatment for obesity [1]. 2. Lu AE58054 hydrochloride (edalopyridine) is a high-affinity selective 5-HT6 receptor antagonist and is currently being developed as an adjunct therapy to acetylcholinesterase inhibitors (AChEIs) for the treatment of mild to moderate Alzheimer's disease (AD). Gamma oscillations in the frontal cortex are pharmacodynamic biomarkers related to cognition; Lu AE58054 hydrochloride enhances donepezil-induced gamma oscillations and may help it play a cognitive-promoting role in donepezil-treated Alzheimer's disease patients [2].
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| Molecular Formula |
C20H20CLF5N2O
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| Molecular Weight |
434.83
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| Exact Mass |
434.118
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| Elemental Analysis |
C, 55.24; H, 4.64; Cl, 8.15; F, 21.85; N, 6.44; O, 3.68
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| CAS # |
467458-02-2
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| Related CAS # |
Idalopirdine; 467459-31-0
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| PubChem CID |
21071391
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| Appearance |
White to off-white solid powder
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| LogP |
6.111
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
29
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| Complexity |
482
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].FC1C([H])=C([H])C2=C(C=1[H])N([H])C([H])=C2C([H])([H])C([H])([H])N([H])C([H])([H])C1C([H])=C([H])C([H])=C(C=1[H])OC([H])([H])C(C([H])(F)F)(F)F
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| InChi Key |
KXOQNPANAFXKTN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19F5N2O.ClH/c21-15-4-5-17-14(11-27-18(17)9-15)6-7-26-10-13-2-1-3-16(8-13)28-12-20(24,25)19(22)23;/h1-5,8-9,11,19,26-27H,6-7,10,12H2;1H
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| Chemical Name |
2-(6-fluoro-1H-indol-3-yl)-N-[[3-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]ethanamine;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2997 mL | 11.4987 mL | 22.9975 mL | |
| 5 mM | 0.4599 mL | 2.2997 mL | 4.5995 mL | |
| 10 mM | 0.2300 mL | 1.1499 mL | 2.2997 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02019394 | Completed | Drug: Lu AE58054 | Healthy | H. Lundbeck A/S | December 2013 | Phase 1 |
| NCT02122692 | Completed | Drug: Lu AE58054 30 mg Drug: Itraconazole |
Healthy Volunteers | H. Lundbeck A/S | March 2014 | Phase 1 |
| NCT02231450 | Completed | Drug: Lu AE58054 encapsulated film-coated tablets |
Heptic Impairment | H. Lundbeck A/S | July 2014 | Phase 1 |
| NCT01019421 | Completed | Drug: Lu AE58054 Drug: Placebo |
Alzheimer's Disease | H. Lundbeck A/S | December 2009 | Phase 2 |
| NCT00810667 | Completed | Drug: Lu AE58054 Drug: Placebo |
Schizophrenia Cognition |
H. Lundbeck A/S | November 2008 | Phase 2 |
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