Auglurant (VU0424238) is a new, selective mGlu5 antagonist that can inhibit rat mGlu5 with IC50 of 11 nM and human mGlu5 with IC50 of 14 nM. Auglurant (VU0424238) penetrates the nervous system.

Physicochemical Properties

Molecular Formula	C16H12FN5O2
Molecular Weight	325.297185897827
Exact Mass	325.098
CAS #	1396337-04-4
PubChem CID	60168069
Appearance	Light yellow to yellow solid powder
LogP	2.831
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	421
Defined Atom Stereocenter Count	0
InChi Key	RBAHIIPVJVMACF-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H12FN5O2/c1-10-4-12(24-13-7-18-9-19-8-13)5-14(21-10)16(23)22-15-3-2-11(17)6-20-15/h2-9H,1H3,(H,20,22,23)
Chemical Name	N-(5-fluoropyridin-2-yl)-6-methyl-4-pyrimidin-5-yloxypyridine-2-carboxamide
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	In HEK293A cells, the IC50 value of auglurant (VU0424238) is 14 nM. Additionally, it binds to a K i value of 4.4 nM in HEK293A cells, which is a recognized allosteric site.
ln Vivo	At an oral dose of 0.8 mg/kg, auglurant (VU0424238) displays 50% mGlu5 PET ligand occupancy in rats and has a clearance of 19.3 mL/min/kg. Additionally, at an oral dosage of 0.06 mg/kg, it exhibits 50% mGlu5 PET ligand occupancy in baboons and a clearance of 15.5 mL/min/kg in cynomolgus monkeys [1].
References	[1]. Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation. J Med Chem. 2017 Jun 22;60(12):5072-5085.

Solubility Data

Solubility (In Vitro)

DMSO : ~22.73 mg/mL (~69.87 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.39 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	3.0741 mL	15.3704 mL	30.7409 mL
	5 mM	0.6148 mL	3.0741 mL	6.1482 mL
	10 mM	0.3074 mL	1.5370 mL	3.0741 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.