VU0650786 is a novel, potent, selective and CNS permeable negative allosteric modulator of metabotropic glutamate receptor subtype 3 (mGlu3 NAM), with an IC50 of 392 nM. In rodents, VU0650786 exhibits anxiolytic and antidepressant properties.

Physicochemical Properties

Molecular Formula	C18H15CLFN5O2
Molecular Weight	387.795405626297
Exact Mass	387.09
CAS #	1809085-30-0
PubChem CID	122190433
Appearance	White to off-white solid powder
LogP	2.4
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	544
Defined Atom Stereocenter Count	1
SMILES	C[C@@H]1CN(C(=O)C2=CC(=NN12)COC3=NC=C(C=C3)Cl)C4=C(N=CC=C4)F
InChi Key	RXRVCJFGSOVYLG-LLVKDONJSA-N
InChi Code	InChI=1S/C18H15ClFN5O2/c1-11-9-24(14-3-2-6-21-17(14)20)18(26)15-7-13(23-25(11)15)10-27-16-5-4-12(19)8-22-16/h2-8,11H,9-10H2,1H3/t11-/m1/s1
Chemical Name	(7R)-2-[(5-chloropyridin-2-yl)oxymethyl]-5-(2-fluoropyridin-3-yl)-7-methyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4-one
Synonyms	VU-0650786; VU 0650786; VU0650786
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

Targets	mGluR3 ( IC50 = 392 nM )
ln Vivo	VU0650786 (VU786) (i.p., 30 mg/kg) diminishes thalamocortical long-term depression (LTD), decreases passive coping in acute models of antidepressant-like activity in inducible cFos-EGFP mice, and increases the proportion of c-Fos-positive cells by about 4-fold[2]. It also improves synaptic strength in cone cell subpopulations[2]. Viu0650786 (compound 106) in rats: pharmacokinetic characteristics[1].
References	[1]. Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents. J Med Chem. 2015 Sep 24;58(18):7485-500. [2]. mGlu2 and mGlu3 Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects. Neuron. 2020 Jan 8;105(1):46-59.e3.

Solubility Data

Solubility (In Vitro)

DMSO: ~250 mg/mL (~644.7 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.36 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 (5.36 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	2.5786 mL	12.8932 mL	25.7865 mL
	5 mM	0.5157 mL	2.5786 mL	5.1573 mL
	10 mM	0.2579 mL	1.2893 mL	2.5786 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.