TCN-201 is a novel, potent, non-competitive and selective antagonist of NMDA receptors containing the NR2A subunit with a pIC50 of 6.8. TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner.

Physicochemical Properties

Molecular Formula	C21H17N3O4FSCL
Molecular Weight	461.89378
Exact Mass	461.061
CAS #	852918-02-6
Related CAS #	852918-02-6;
PubChem CID	4787937
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.625
LogP	4.13
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	31
Complexity	719
Defined Atom Stereocenter Count	0
InChi Key	FYIBXBFDXNPBSF-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H17ClFN3O4S/c22-18-12-17(10-11-19(18)23)31(29,30)24-13-14-6-8-16(9-7-14)21(28)26-25-20(27)15-4-2-1-3-5-15/h1-12,24H,13H2,(H,25,27)(H,26,28)
Chemical Name	N-[[4-(benzamidocarbamoyl)phenyl]methyl]-3-chloro-4-fluorobenzenesulfonamide
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 Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.(2). This product is not stable in solution, please use freshly prepared working solution for optimal results.
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	Compound 1, TCN 201, has a pIC50 of <4.3 and 6.8, respectively, making it more selective for GluN1/GluN2A NMDAR than GluN1/GluN2B NMDAR [1]. In oocytes, TCN 201 (10 μM) only modestly suppresses GluN1/GluN2B NMDAR-mediated currents [2]. In oocytes, TCN 201 (10-30 μM) exhibits a more powerful antagonistic effect on NMDAR-mediated responses, which is dependent on isoform and glycine [2]. In oocytes, NMDAR-mediated responses are not entirely blocked by TCN 201 (0.1-100 μM) [2]. In rat cortical neurons, TCN 201 (10 μM) antagonistic activity against NMDAR-mediated currents is inversely linked with its ifenprodil sensitivity [2]. In chick retina, cortical spreading depression (CSD) is inhibited by TCN 201 (1-9 μM) [3].
ln Vivo	Rats with CSD exhibit an insufficient response to TCN-201 (10 mg/kg; intraperitoneal injection) regarding the blood oxygenation level-dependent (BOLD) response [4].
References	[1]. Identification and characterization of novel NMDA receptor antagonists selective for NR2A- over NR2B-containing receptors. J Pharmacol Exp Ther. 2010 Dec; 335(3): 636-44. [2]. TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner. Neuropharmacology. 2012 Sep; 63(3): 441-9. [3]. NR2A contributes to genesis and propagation of cortical spreading depression in rats. Sci Rep. 2016 Mar 22;6:23576. [4]. Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI. Neuropharmacology. 2015 Jun; 93:164-70.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~541.25 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.50 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 20.8 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: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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: ≥ 2.08 mg/mL (4.50 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1650 mL	10.8251 mL	21.6502 mL
	5 mM	0.4330 mL	2.1650 mL	4.3300 mL
	10 mM	0.2165 mL	1.0825 mL	2.1650 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.