| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
OX2 Receptor
Firazorexton targets the orexin type 2 receptor (OX2R) as a highly selective agonist. It has an EC50 of 19 nM for OX2R. Orexin receptors are involved in the regulation of wakefulness, sleep-wake transitions, and appetite. By activating OX2R, Firazorexton promotes wake-promoting signaling pathways in the central nervous system. Its oral bioavailability and brain penetration make it suitable for in vivo studies of sleep-wake regulation. Its selectivity for OX2R over other orexin receptors makes it a valuable tool for studying the specific roles of this receptor. |
|---|---|
| ln Vitro |
In vitro studies demonstrate that Firazorexton (TAK-994 free base) is a highly selective OX2R agonist with an EC50 of 19 nM. It activates OX2R with high potency and selectivity, promoting wake-promoting signaling pathways. The compound's oral bioavailability and brain penetration have been demonstrated in preclinical studies. Detailed in vitro characterization data, including receptor binding and functional assays, are available in the primary literature. The compound's selectivity for OX2R makes it a valuable tool for studying orexin receptor pharmacology and for developing treatments for sleep disorders.
|
| ln Vivo |
In vivo studies of Firazorexton have demonstrated its efficacy in promoting wakefulness and improving narcolepsy-like symptoms. In normal mice, Firazorexton promotes wakefulness. In narcolepsy mouse models, it improves arousal fragmentation and suppresses cataplexy-like episodes. The compound's oral bioavailability and brain penetration support its use in in vivo studies. Specific in vivo efficacy data, including effects on sleep-wake parameters, are available in the primary literature. The compound has been investigated in clinical trials for narcolepsy. Further studies are ongoing to characterize its full therapeutic potential.
|
| Enzyme Assay |
For OX2R binding assays, membrane preparations from cells expressing recombinant OX2R are incubated with radiolabeled ligands and varying concentrations of Firazorexton. Non-specific binding is determined using excess unlabeled reference compounds. Following incubation at appropriate temperature (typically 25°C for 60-90 minutes), bound and free radioligands are separated by rapid filtration through glass fiber filters. Filters are washed and radioactivity counted by liquid scintillation. IC50 or Ki values are calculated from competition curves. For functional assays, receptor activation is measured by calcium flux or IP3 accumulation assays.
|
| Cell Assay |
For in vitro cellular assays, cell lines expressing OX2R (e.g., CHO or HEK293 cells) are cultured in appropriate media under standard conditions (37°C, 5% CO2). Firazorexton is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations. Receptor activation is assessed by measuring intracellular calcium flux using fluorescent indicators or by measuring downstream signaling pathways. Cell viability and cytotoxicity can be assessed using standard assays. Each concentration is tested in replicate wells with vehicle controls and positive controls (e.g., orexin-A).
|
| Animal Protocol |
For in vivo animal studies, Firazorexton is typically administered orally (by gavage) due to its oral bioavailability. In normal mice, the compound promotes wakefulness. In narcolepsy mouse models, it improves arousal fragmentation and suppresses cataplexy-like episodes. Sleep-wake parameters are monitored using EEG/EMG recordings. For pharmacokinetic studies, blood and brain tissue samples are collected at predetermined time points post-administration, and drug concentrations are quantified by LC-MS/MS. All procedures must follow institutional animal care and use committee guidelines.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Firazorexton indicate it is orally bioavailable and brain-penetrant. The compound has a CAS number of 2274802-95-6. Storage: typically at -20°C for powder; in solvent at -80°C. Solubility: soluble in DMSO and other organic solvents. As a small-molecule OX2R agonist, it is expected to have favorable oral bioavailability and blood-brain barrier penetration. Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are reported in the primary literature.
|
| Toxicity/Toxicokinetics |
According to available safety information, Firazorexton is intended for research purposes only and is not for human therapeutic use outside of clinical research. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. Clinical toxicity data may be available from clinical trial reports.
|
| References |
|
| Additional Infomation |
Firazorexton is being studied in the clinical trial NCT04096560 (the TAK-994 study, which is a study of adult patients with type 1 and type 2 narcolepsy).
Firazorexton (TAK-994 free base) is an orally bioavailable, brain-penetrant, highly selective OX2R agonist with an EC50 of 19 nM. It promotes wakefulness in normal mice and improves narcolepsy-like symptoms in mouse models. It has the potential to improve narcolepsy-like symptoms. It has a CAS number of 2274802-95-6. It is for research use only with no regulatory approvals reported. |
| Molecular Formula |
C22H25F3N2O4S
|
|---|---|
| Molecular Weight |
470.505115270615
|
| Exact Mass |
470.148
|
| CAS # |
2274802-95-6
|
| Related CAS # |
Firazorexton hydrate;2861934-86-1;(2R,3R)-Firazorexton;2692692-00-3
|
| PubChem CID |
137460733
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
766
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
S(C)(N[C@H]1CCN(C(C(C)(C)O)=O)[C@H]1CC1C=CC=C(C2C=C(C=C(C=2)F)F)C=1F)(=O)=O
|
| InChi Key |
VOSAWOSMGPKQEQ-OALUTQOASA-N
|
| 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-/m0/s1
|
| Chemical Name |
N-[(2S,3S)-2-[[3-(3,5-difluorophenyl)-2-fluorophenyl]methyl]-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]methanesulfonamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 250 mg/mL (531.34 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
