| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
The primary targets of ACT-462206 are the orexin type 1 (OX1) and type 2 (OX2) receptors. It acts as a dual antagonist, blocking both receptor subtypes. Orexin peptides (orexin-A and -B) are neuropeptides that regulate arousal, wakefulness, and reward. By antagonizing both OX1 and OX2, ACT-462206 can modulate the entire orexinergic system, affecting various physiological processes. Its balanced affinity for both receptors distinguishes it from selective OX1 antagonists.
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| ln Vitro |
Orexin receptor type 1 (OX1) and type 2 (OX2) are two closely related G protein-coupled receptors (GPCRs) to which orexin can bind after being released in an axon terminal in a Ca2+-sensitive manner[1]. 17 nM (hOX1), 2.4 nM (hOX2), 28 nM (rOX1), 9.9 nM (rOX2), 27 nM (dOX1), and 4.2 nM (dOX2) are the binding affinities of ACT-462206 and Kb [1]. With IC50s of 60 nM (hOX1), 11 nM (hOX2), 48 nM (rOX1), 9.6 nM (rOX2), 68 nM (dOX1), and 26 nM (dOX2), ACT-462206 suppresses Orexin activity [1]. CYP450 3A4T and 3A4M are inhibited by ACT-462206, with IC50 values of 15 μM and 29 μM, respectively[1].
In vitro, ACT-462206 demonstrates potent dual orexin receptor antagonism. It has IC₅₀ values of 60 nM for OX1 and 11 nM for OX2, indicating higher potency at OX2. The Kb values are 250 nM for OX1 and 48 nM for OX2. These values are determined in functional assays measuring orexin-induced calcium mobilization or other downstream signals. The compound's ability to block both receptors is confirmed in these cell-based assays. |
| ln Vivo |
ACT-462206 (Compound 24) (100 mg/kg; oral; 3-hour sampling) has concentrations in the brain and plasma of male Wistar rats of 1219 ng/g and 2267 ng/mL, respectively, indicating that it can cross the blood-brain barrier [1]. In male Wistar rats and male Beagle dogs, ACT-462206 (10-300 mg/kg; oral; single dose) reduces arousal and increases non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. 1]. The oral medication ACT-462206 (100, 300 mg/kg; single dose) has anxiolytic-like effects on rats, improving the startle reflex, decreasing movement, body temperature, and heart rate increases brought on by social stress [1]. Different species' pharmacokinetics [1]: Route dose (mg/kg), AUC (ng·h/mL), CL (mL/min/kg), Vss (L/kg), t1/2 (h), cmax (ng/mL), tmax (h), F1/2 (%) Rat iv 1 586 29 1.8 1.9 / / / po 10 2310 / / / 1600 0.5 39 Dog iv 1 1490 11 1.4 1.7 / / / po 3 2750 / / / 426 0.5 52
In vivo, ACT-462206 exhibits anxiolytic-like effects and may also influence sleep-wake architecture. As an orally active and brain-penetrant compound, it is used in rodent models to study the behavioral and physiological consequences of dual orexin receptor blockade. Its effects on anxiety, stress responses, and feeding behavior have been investigated. The compound's profile is distinct from selective OX1 or OX2 antagonists, making it a valuable tool. |
| Enzyme Assay |
In vitro receptor binding studies for ACT-462206 measure its affinity for both OX1 and OX2 receptors. Radioligand competition assays using membrane preparations from cells expressing the human receptors are performed. The compound competes with a labeled orexin peptide, and IC₅₀ values are derived. The selectivity ratio (OX1/OX2) is calculated to characterize its binding profile. These studies are essential for confirming its dual antagonism.
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| Cell Assay |
In vitro cell-based functional assays for ACT-462206 evaluate its ability to block orexin-induced signaling. Cells expressing OX1 or OX2 receptors are loaded with a calcium-sensitive dye and stimulated with an orexin agonist. The compound's inhibition of the calcium response is measured, and IC₅₀ values are determined. These assays are performed in parallel to confirm the compound's functional antagonism at both receptor subtypes.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rat[1]
Doses: 0, 10, 30, 100, 300 mg/kg Route of Administration: po (oral gavage); single dose Experimental Results: shortened the first sustained non-rapid eye movement sleep (60 seconds) and latency to first sustained REM sleep (30 seconds). Total arousal time and behavioral home cage activity were dose-dependently diminished (one-way ANOVA; p < 0.001), while REM and non-REM sleep time were increased. In vivo animal studies for ACT-462206 typically involve behavioral tests in rodents. For anxiety, the elevated plus maze or light-dark box test is used. For sleep-wake studies, electroencephalography (EEG) and electromyography (EMG) recordings are performed to assess changes in sleep architecture. The compound is administered orally, and dose-response relationships are established. Pharmacodynamic endpoints include plasma and brain drug levels. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of ACT-462206 are characterized by oral bioavailability and good brain penetration. Its molecular weight is 388.5 g/mol. The compound is typically stored as a powder at -20°C. Solubility in DMSO is reported. Further pharmacokinetic parameters such as half-life, Cmax, and clearance would be available from the supplier's data or published studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of ACT-462206 has not been fully published. As a research compound, it is intended for non-human use. The safety margin would be determined in preclinical toxicology studies. Common side effects of orexin receptor antagonists may include sleepiness and fatigue. Standard safety precautions for handling potent pharmacological agents should be observed.
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| References | |
| Additional Infomation |
Additional information: ACT-462206 has the CAS number 1361321-96-1. Its molecular formula is C₂₀H₂₄N₂O₄S. It is also known as ACT-462206. The compound is supplied as a solid. It is intended for research purposes only and is not for human therapeutic use. This product is for research use only and is not approved for clinical or therapeutic applications.
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| Molecular Formula |
C20H24N2O4S
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| Molecular Weight |
388.480564117432
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| Exact Mass |
388.146
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| CAS # |
1361321-96-1
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| PubChem CID |
40924317
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| Appearance |
White to off-white solid powder
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| LogP |
4.195
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
600
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(=CC(=C1)NC(=O)[C@@H]2CCCN2S(=O)(=O)C3=CC=C(C=C3)OC)C
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| InChi Key |
NHPQGZOBHSVTAQ-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C20H24N2O4S/c1-14-11-15(2)13-16(12-14)21-20(23)19-5-4-10-22(19)27(24,25)18-8-6-17(26-3)7-9-18/h6-9,11-13,19H,4-5,10H2,1-3H3,(H,21,23)/t19-/m0/s1
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| Chemical Name |
(2S)-N-(3,5-dimethylphenyl)-1-(4-methoxyphenyl)sulfonylpyrrolidine-2-carboxamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ≥ 100 mg/mL (~257.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.44 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 (6.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5741 mL | 12.8707 mL | 25.7414 mL | |
| 5 mM | 0.5148 mL | 2.5741 mL | 5.1483 mL | |
| 10 mM | 0.2574 mL | 1.2871 mL | 2.5741 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 |
| NCT01954589 | Completed | Drug: ACT-462206 5 mg Drug: ACT-462206 25 mg |
Safety Tolerability |
Idorsia Pharmaceuticals Ltd. | November 2011 | Phase 1 |
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