Tonabersat (also known as SB-220453), a benzopyran derivative, is a novel and potent gap-junction modulator used for the prevention of migraine. Tonabersat inhibits cortical spreading depression (CSD) and therefore might be able to inhibit the early migraine mechanisms. Treatment with either Tonabersat (10 mg/kg) or Meclofenamate (20 mg/kg) as single agents significantly inhibit progression of metastatic lesions. Addition of carboplatin to either agent profoundly inhibits brain metastasis.

Physicochemical Properties

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)

Biological Activity

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].
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].
References	[1]. Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine. Cephalalgia. 2009 Nov;29 Suppl 2:17-27. [2]. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016 May 18;533(7604):493-8. [3]. Tonabersat Prevents Inflammatory Damage in the Central Nervous System by Blocking Connexin43 Hemichannels. Neurotherapeutics. 2017 May 30.
Additional Infomation	Drug Indication Investigated for use/treatment in migraine and cluster headaches.

Solubility Data

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. 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. 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. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

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.