ACT-462206
Based on 1 Customer Validation
ACT-462206 is an orally active and potent dual Orexin 1/Orexin 2 receptor antagonist with IC50s of 60 nM (Orexin 1) and 11 nM (Orexin 2), respectively. ACT-462206 exhibits brain penetration properties, and can be used for insomnia, stress/anxiety-related disorders and addiction research.
For research use only. We do not sell to patients.
- Purity: 99.54%
- CAS No.: 1361321-96-1
- Formula: C20H24N2O4S
- Molecular Weight:388.48
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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All Orexin Receptor (OX Receptor) Isoforms
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Biological Activity
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OX2 |
OX1 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | IC50 |
11 nM
Compound: 21, ACT-462206
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Antagonist activity at recombinant orexin-2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of orexin-A-induced Ca2+ flux preincubated for 120 mins followed by orexin-A induction measured every 1 sec by FLIPR assay
Antagonist activity at recombinant orexin-2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of orexin-A-induced Ca2+ flux preincubated for 120 mins followed by orexin-A induction measured every 1 sec by FLIPR assay
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[PMID: 26045032] |
| CHO | IC50 |
11 nM
Compound: 22; ACT-462206
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Antagonist activity at human OX2R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release by FLIPR assay
Antagonist activity at human OX2R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release by FLIPR assay
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[PMID: 26317591] |
| CHO | IC50 |
60 nM
Compound: 21, ACT-462206
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Antagonist activity at recombinant orexin-1 receptor (unknown origin) expressed in CHO cells assessed as inhibition of orexin-A-induced Ca2+ flux preincubated for 120 mins followed by orexin-A induction measured every 1 sec by FLIPR assay
Antagonist activity at recombinant orexin-1 receptor (unknown origin) expressed in CHO cells assessed as inhibition of orexin-A-induced Ca2+ flux preincubated for 120 mins followed by orexin-A induction measured every 1 sec by FLIPR assay
|
[PMID: 26045032] |
| CHO | IC50 |
60 nM
Compound: 22; ACT-462206
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Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release by FLIPR assay
Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release by FLIPR assay
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[PMID: 26317591] |
Orexins are released in a Ca2+-sensitive manner at axonal terminals and can then bind to two closely related G-protein-coupled receptors (GPCRs): orexin receptor type 1 (OX1) and orexin receptor type 2 (OX2)[1].
ACT-462206 shows binding affinity with Kbs of 17 nM (hOX1), 2.4 nM (hOX2), 28 nM (rOX1), 9.9 nM (rOX2), 27 nM (dOX1), 4.2 nM (dOX2), respectively[1].
ACT-462206 inhibits Orexin activity with IC50s of 60 nM (hOX1), 11 nM (hOX2), 48 nM (rOX1), 9.6 nM (rOX2), 68 nM (dOX1), 26 nM (dOX2), respectively[1].
ACT-462206 inhibits CYP450 3A4T and 3A4M with IC50s of 15 μM and 29 μM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
ACT-462206 (10-300 mg/kg; p.o.; single dose) shows sleep-promoting effects in male Wistar rats and in male Beagle dogs, with decreasing wakefulness and increasing non-rapid eye movement (non-REM) and REM sleep[1].
ACT-462206 (100, 300 mg/kg; p.o.; single dose) exerts anxiolytic-like effects, decreases the fear-potentiated startle reflexes in response to a sudden loud noise in rats, reduces the socialstress-induced increases of locomotion, body temperature, and heart rate[1].
Pharmacokinetics in different species[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 | i.v. | 1 | 586 | 29 | 1.8 | 1.9 | / | / | / |
| p.o. | 10 | 2310 | / | / | / | 1600 | 0.5 | 39 | |
| dog | i.v. | 1 | 1490 | 11 | 1.4 | 1.7 | / | / | / |
| p.o. | 3 | 2750 | / | / | / | 426 | 0.5 | 52 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Wistar rats[1]
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Dosage:0, 10, 30, 100, 300 mg/kg
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Administration:Oral gavage; single dose
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Result:Decreased the latency to the first persistent episode of non-REM sleep (60 s) and the first persistent episode of REM sleep (30 s).
Dose-dependently decreased total wake time and behavioral home cage activity (one-way ANOVA; p <0.001), while increasing REM and non-REM sleep times.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1361321-96-1
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Appearance Solid
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Molecular Weight 388.48
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Formula C20H24N2O4S
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Color White to off-white
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SMILES
O=C([C@H]1N(S(=O)(C2=CC=C(OC)C=C2)=O)CCC1)NC3=CC(C)=CC(C)=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
DMSO : ≥ 100 mg/mL (257.41 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.44 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (282 KB)
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SDS (392 KB)
- English - EN (392 KB)
- Français - FR (392 KB)
- Deutsch - DE (392 KB)
- Norwegian - NO (392 KB)
- Español - ES (392 KB)
- Swedish - SV (392 KB)
- Italian - IT (392 KB)
- Korean - KR (392 KB)
- Portuguese - PT (392 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.5741 mL | 12.8707 mL | 25.7414 mL | 64.3534 mL |
| 5 mM | 0.5148 mL | 2.5741 mL | 5.1483 mL | 12.8707 mL | |
| 10 mM | 0.2574 mL | 1.2871 mL | 2.5741 mL | 6.4353 mL | |
| 15 mM | 0.1716 mL | 0.8580 mL | 1.7161 mL | 4.2902 mL | |
| 20 mM | 0.1287 mL | 0.6435 mL | 1.2871 mL | 3.2177 mL | |
| 25 mM | 0.1030 mL | 0.5148 mL | 1.0297 mL | 2.5741 mL | |
| 30 mM | 0.0858 mL | 0.4290 mL | 0.8580 mL | 2.1451 mL | |
| 40 mM | 0.0644 mL | 0.3218 mL | 0.6435 mL | 1.6088 mL | |
| 50 mM | 0.0515 mL | 0.2574 mL | 0.5148 mL | 1.2871 mL | |
| 60 mM | 0.0429 mL | 0.2145 mL | 0.4290 mL | 1.0726 mL | |
| 80 mM | 0.0322 mL | 0.1609 mL | 0.3218 mL | 0.8044 mL | |
| 100 mM | 0.0257 mL | 0.1287 mL | 0.2574 mL | 0.6435 mL |
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