GNE 0723 is a novel, potent, brain permeable positive allosteric modulator (PAM) and GluN2A subunit-selective of NMDAR, with an EC50 of 21 nM for GluN2A, 7.4 and 6.2 μM for GluN2C and GluN2D, respectively. The N-methyl-d-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca2+ and Na+. NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. GNE-0723 is a and brain-penetrant positive allosteric modulatorof NMDARs.

Physicochemical Properties

Molecular Formula	C16H8CLF6N5OS
Molecular Weight	467.776041030884
Exact Mass	467.004
CAS #	1883518-31-7
PubChem CID	127046129
Appearance	White to yellow solid powder
Density	1.8±0.1 g/cm3
Boiling Point	505.2±60.0 °C at 760 mmHg
Flash Point	259.4±32.9 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.680
LogP	2.89
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	935
Defined Atom Stereocenter Count	2
SMILES	C1[C@H]([C@@H]1C2=C(SC3=NC(=CC(=O)N23)CN4C(=CC(=N4)C(F)(F)F)Cl)C(F)(F)F)C#N
InChi Key	FTIBNGABJNFFAI-POYBYMJQSA-N
InChi Code	InChI=1S/C16H8ClF6N5OS/c17-10-3-9(15(18,19)20)26-27(10)5-7-2-11(29)28-12(8-1-6(8)4-24)13(16(21,22)23)30-14(28)25-7/h2-3,6,8H,1,5H2/t6-,8+/m0/s1
Chemical Name	(1R,2R)-2-[7-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-5-oxo-2-(trifluoromethyl)-[1,3]thiazolo[3,2-a]pyrimidin-3-yl]cyclopropane-1-carbonitrile
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	GNE-0723 is an NMDAR positive allosteric modulator that penetrates the brain, and its EC50 values are 21 nM for GluN2A, 7.4 μM for GluN2C, and 6.2 μM for GluN2D [1].
References	[1]. GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. ACS Med Chem Lett. 2016 Oct 31;8(1):84-89.

Solubility Data

Solubility (In Vitro)

DMSO : ~190 mg/mL (~406.17 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 4.75 mg/mL (10.15 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 47.5 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: ≥ 4.75 mg/mL (10.15 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 47.5 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: ≥ 4.75 mg/mL (10.15 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 47.5 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	2.1378 mL	10.6888 mL	21.3776 mL
	5 mM	0.4276 mL	2.1378 mL	4.2755 mL
	10 mM	0.2138 mL	1.0689 mL	2.1378 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.