| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
OX2R (orexin type 2 receptor). As the free base form of TAK-994, this compound acts as a selective OX2R agonist, activating orexin signaling to promote wakefulness.
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|---|---|
| ln Vitro |
As the free base form of the same active pharmaceutical ingredient, this isomer is expected to exhibit essentially the same pharmacological activity as firazorexton (TAK-994), i.e., potent OX2R agonism with high selectivity over OX1R. No comparative potency data between the free base and the hydrate form are available.
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| ln Vivo |
No specific in vivo activity data are reported for this isomer. As the free base of TAK-994, it would be expected to exhibit the same efficacy as TAK-994 in preclinical narcolepsy models, i.e., improving maintenance of wakefulness, reducing cataplexy episodes, and increasing wakefulness time in orexin-deficient mice. However, no published studies specifically using the free base are available.
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| Enzyme Assay |
Cell-free functional assays for OX2R agonism using this compound would follow the same procedures as for firazorexton. Membranes from CHO-K1 cells expressing human OX2R are incubated with 35S-GTPgammaS and increasing concentrations of the test compound in assay buffer (20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, pH 7.4) for 60 min at 25degC. Bound radioactivity is separated by filtration, and EC50 values are determined by nonlinear regression.
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| Cell Assay |
CHO-K1 cells expressing human OX2R are loaded with a calcium-sensitive fluorescent dye. The test compound is added at increasing concentrations (0.1 nM to 10 uM), and intracellular calcium flux is measured using a FLIPR. The EC50 for OX2R activation is determined from dose-response curves. This isomer is expected to have an EC50 similar to that of firazorexton (sub-nanomolar range).
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| Animal Protocol |
No specific in vivo animal protocols have been published for this isomer. For the TAK-994 free base, expected in vivo protocols would include oral administration to orexin/ataxin-3 transgenic narcolepsy mice at doses of 3-30 mg/kg, with wakefulness measured by EEG/EMG recordings. Blood and brain samples would be collected at various time points for PK analysis by LC-MS/MS. The free base is the active form of the drug.
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| ADME/Pharmacokinetics |
No specific PK data are reported for the free base isomer. As the active form of TAK-994, the free base is expected to share the same PK properties as the hydrate form: oral bioavailability, brain-penetration capability, dose-proportional exposure, and Tmax around 1-2 hours post-administration. The free base is the pharmacologically active species that crosses the blood-brain barrier to engage OX2R.
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| Toxicity/Toxicokinetics |
No toxicity data are specifically reported for this isomer. The safety profile would be expected to match that of TAK-994 hydrate, which includes hepatotoxicity and nephrotoxicity that led to termination of clinical development. Renal and urinary adverse events and drug-induced liver injury have been reported for TAK-994. This free base form would carry the same safety liabilities.
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| References | |
| Additional Infomation |
Other information: (2R,3R)-Firazorexton is the free base form of TAK-994 and contains two chiral centers (the 2R,3R configuration). The CAS number is 2692692-00-3. TAK-994 is the hydrate form. This isomer is available for research use only and is not for clinical use. The parent compound TAK-994 was discontinued due to liver and kidney toxicity. This compound is a research chemical and not an FDA-approved drug.
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| Molecular Formula |
C22H25F3N2O4S
|
|---|---|
| Molecular Weight |
470.505115270615
|
| Exact Mass |
470.148
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| CAS # |
2692692-00-3
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| Related CAS # |
Firazorexton;2274802-95-6;Firazorexton hydrate;2861934-86-1
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| PubChem CID |
169450759
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| Appearance |
White to off-white solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
766
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC(C)(C(=O)N1CC[C@H]([C@H]1CC2=C(C(=CC=C2)C3=CC(=CC(=C3)F)F)F)NS(=O)(=O)C)O
|
| InChi Key |
VOSAWOSMGPKQEQ-RTBURBONSA-N
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| InChi Code |
InChI=1S/C22H25F3N2O4S/c1-22(2,29)21(28)27-8-7-18(26-32(3,30)31)19(27)11-13-5-4-6-17(20(13)25)14-9-15(23)12-16(24)10-14/h4-6,9-10,12,18-19,26,29H,7-8,11H2,1-3H3/t18-,19-/m1/s1
|
| Chemical Name |
N-[(2R,3R)-2-[[3-(3,5-difluorophenyl)-2-fluorophenyl]methyl]-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]methanesulfonamide
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1254 mL | 10.6268 mL | 21.2535 mL | |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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.
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