| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Tonabersat targets gap junctions, which are channels that allow direct communication between adjacent cells. It acts as a gap junction modulator, specifically inhibiting cortical spreading depression (CSD). CSD is a wave of neuronal depolarization that is believed to be a key mechanism in migraine with aura.
|
|---|---|
| ln Vitro |
Tonabersat is a brand-new benzopyran derivative that has the ability to block early migraine mechanisms by blocking cortical spreading depression (CSD) [1].
In vitro, Tonabersat blocks cortical spreading depression (CSD), a key mechanism involved in migraine initiation. It modulates gap junction communication between trigeminal ganglion neurons and glial cells and inhibits neurogenic inflammation. It demonstrates potent activity in neuronal cell models. |
| ln Vivo |
Lesions with metastases are considerably slowed down in their progression by tonabersat (10 mg/kg). NSC 241240 dramatically reduces brain metastases when added to either medication [2].
In vivo, treatment with Tonabersat (10 mg/kg) significantly inhibits progression of metastatic lesions. Addition of carboplatin to Tonabersat profoundly inhibits brain metastasis. Lesions with metastases are considerably slowed down in their progression by Tonabersat. It has been studied for the treatment of migraines and cluster headaches. |
| Enzyme Assay |
The in vitro receptor binding assay for Tonabersat involves characterizing its binding to its unique stereoselective binding site in the central nervous system. Competition binding experiments are performed using radiolabeled Tonabersat or related compounds. Functional assays measuring gap junction communication or CSD inhibition are also conducted.
|
| Cell Assay |
In vitro cell-based assays are performed using neuronal cell lines or primary neuronal cultures. Cells are treated with Tonabersat, and gap junction communication is measured using dye transfer assays or electrophysiological techniques. The compound's ability to inhibit CSD is assessed in brain slice preparations. IC₅₀ values are determined.
|
| Animal Protocol |
In vivo animal experiments for Tonabersat have been conducted in models of migraine and brain metastasis. Animals are administered the compound orally or via other routes, and CSD is induced and measured. The compound's effects on pain behavior, neuronal activity, and metastatic progression are assessed. It has been studied in clinical trials for migraine prevention.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Tonabersat have been characterized in preclinical species and humans. It is orally bioavailable and penetrates the central nervous system. Detailed PK parameters such as half-life, clearance, volume of distribution, and oral bioavailability are determined from plasma and brain concentration-time profiles.
|
| Toxicity/Toxicokinetics |
In clinical studies, Tonabersat was generally well-tolerated with an acceptable safety profile. Standard toxicology assessments were conducted to support clinical development. The compound has been evaluated in clinical trials for migraine prevention. No significant safety concerns were reported.
|
| References |
|
| Additional Infomation |
Drug Indication
This drug has been studied for the treatment of migraines and cluster headaches. Tonabersat is a first-in-class gap junction modulator with a unique mechanism of action for migraine prevention. It inhibits cortical spreading depression (CSD), a key early event in migraine pathophysiology. It has been studied in clinical trials but has not been approved for clinical use. |
| Molecular Formula |
C20H19NO4FCL
|
|---|---|
| Molecular Weight |
391.82056
|
| Exact Mass |
391.099
|
| CAS # |
175013-84-0
|
| PubChem CID |
6918324
|
| Appearance |
White to yellow solid powder
|
| Density |
1.38g/cm3
|
| Boiling Point |
554.5ºC at 760 mmHg
|
| Flash Point |
289.2ºC
|
| Vapour Pressure |
3.94E-13mmHg at 25°C
|
| Index of Refraction |
1.612
|
| LogP |
4.075
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
586
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC(=O)C1=CC2=C(C=C1)OC([C@H]([C@H]2NC(=O)C3=CC(=C(C=C3)F)Cl)O)(C)C
|
| InChi Key |
XLIIRNOPGJTBJD-ROUUACIJSA-N
|
| InChi Code |
InChI=1S/C20H19ClFNO4/c1-10(24)11-5-7-16-13(8-11)17(18(25)20(2,3)27-16)23-19(26)12-4-6-15(22)14(21)9-12/h4-9,17-18,25H,1-3H3,(H,23,26)/t17-,18-/m0/s1
|
| Chemical Name |
N-((3S,4S)-6-Acetyl-3-hydroxy-2,2-dimethylchroman-4-yl)-3-chloro-4-fluorobenzamide
|
| Synonyms |
SB220453; SB 220453; SB-220453
|
| 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 : ≥ 100 mg/mL (~255.22 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.38 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 (6.38 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.38 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5522 mL | 12.7610 mL | 25.5219 mL | |
| 5 mM | 0.5104 mL | 2.5522 mL | 5.1044 mL | |
| 10 mM | 0.2552 mL | 1.2761 mL | 2.5522 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.
 Inhibition of gap junction activity controls brain metastatic outgrowth.Nature.2016 May 26;533(7604):493-498. |
|---|
 Inhibition of Gap Junction Activity Prevents Brain Metastatic Outgrowth.Nature.2016 May 26;533(7604):493-498. |
 Gap junctions induce cytosolic dsDNA response in astrocytes.Nature.2016 May 26;533(7604):493-498. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA