VU6012962 is a novel, potent, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu7) negative allosteric modulator (NAM) with an IC50 of 347 nM. It reaches exposure in cerebral spinal fluid (CSF) 2.5 times higher than the in vitro IC50 at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models. It is suitable for use as an in vivo tool compound.

Physicochemical Properties

Molecular Formula	C21H19F3N4O4
Molecular Weight	448040
Exact Mass	448.135
Elemental Analysis	C, 56.25; H, 4.27; F, 12.71; N, 12.50; O, 14.27
CAS #	2313526-86-0
Related CAS #	N/A
PubChem CID	137321168
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.605
LogP	3.94
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	8
Heavy Atom Count	32
Complexity	637
Defined Atom Stereocenter Count	0
SMILES	FC(OC1C([H])=C([H])C(=C(C=1[H])N([H])C(C1C([H])=C([H])C(=C(C=1[H])OC([H])([H])[H])OC([H])([H])C1([H])C([H])([H])C1([H])[H])=O)N1C([H])=NC([H])=N1)(F)F
InChi Key	IQNLJJLZIVCGFI-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H19F3N4O4/c1-30-19-8-14(4-7-18(19)31-10-13-2-3-13)20(29)27-16-9-15(32-21(22,23)24)5-6-17(16)28-12-25-11-26-28/h4-9,11-13H,2-3,10H2,1H3,(H,27,29)
Chemical Name	4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]benzamide
Synonyms	VU6012962; VU-6012962; VU 6012962
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	mGlu7 ( IC50 = 347 nM )
ln Vitro	VU6012962 is highly mGlu7-specific in contrast to the other seven mGlu receptor subtypes[1].
ln Vivo	VU6012962 (1–10 mg/kg; intraperitoneal injection; given 60 minutes before testing) reduces mice's anxiety in the elevated zero maze (EZM) test[1].
Animal Protocol	C57Bl/6J male mice (8 weeks old) 1, 3, and 10 mg/kg I.p. injections; 60 minutes prior to testing
References	[1]. Discovery of an orally bioavailable and Central Nervous System (CNS) penetrant mGlu7 NegativeAllosteric Modulator (NAM) in vivo tool compound: N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962). J Med Chem. 2019 Jan 4.

Solubility Data

Solubility (In Vitro)

DMSO: ~125 mg/mL (~278.8 mM) Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.64 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	0.0022 mL	0.0112 mL	0.0223 mL
	5 mM	446.3887 nL	0.0022 mL	0.0045 mL
	10 mM	223.1944 nL	0.0011 mL	0.0022 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.