MGLU7 ANTAGONIST XAP044

General description

A blood-brain barrier permeable and bioavailable chromenone compound that acts as a potent, selective, and reversible antagonist of mGlu7 receptor (IC₅₀ = 3.5 and 2.8 µM for mGlu7a and mGlu7b in CHO cells). Docks within the Venus flytrap domain (VFTD) close to the binding site of L-glutamate and functions as an orthosteric-like antagonist. Reduces DL-2-amino-4-phosphonobutyric acid (DL-AP4)-induced activation of human mGlu7b receptor (IC₅₀ = 2.8 µM), but does not affect DL-AP4-induced activation of [³⁵S]GTPγS binding by mGlu4 and mGlu6. Shown to diminish [³⁵S]GTPγS binding by the human mGlu7/6 chimeric receptor harboring mGlu7 VFTD (IC₅₀ = 2.5 µM). Displays weak binding affinity towards mGlu5 and mGlu8 receptors (IC₅₀ >20 and 33 µM, respectively) and has no effect on GABA-induced activation of [³⁵S]GTPγS binding by GABA-B receptors. Displays antidepressant and anxiolytic-like properties and selectively blocks long-term potentiation (LTP) in the lateral amygdala of wild type (IC₅₀ = 88 nM), but not of mGlu7- deficient mice.

A blood-brain barrier permeable and bioavailable chromenone compound that acts as a potent, selective, and reversible antagonist of mGlu7 receptor (IC₅₀ = 3.5 and 2.8 µM for mGlu7a and mGlu7b in CHO cells). Docks within the Venus flytrap domain (VFTD) close to the binding site of L-glutamate and functions as an orthosteric-like antagonist. Reduces DL-2-amino-4-phosphonobutyric acid (DL-AP4)-induced activation of human mGlu7b receptor (IC₅₀ = 2.8 µM), but does not affect DL-AP4-induced activation of [³⁵S]GTPγS binding by mGlu4 and mGlu6. Shown to diminish [³⁵S]GTPγS binding by the human mGlu7/6 chimeric receptor harboring mGlu7 VFTD (IC₅₀ = 2.5 µM). Displays weak binding affinity towards mGlu5 and mGlu8 receptors (IC₅₀ >20 and 33 µM, respectively) and has no effect on GABA-induced activation of [³⁵S]GTPγS binding by GABA-B receptors. Displays antidepressant and anxiolytic-like properties and selectively blocks long-term potentiation (LTP) in the lateral amygdala of wild type (IC₅₀ = 88 nM), but not of mGlu7- deficient mice.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
mGlu7R

Reversible: yes

Target IC₅₀: 3.5 and 2.8 &micro

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Gee, C.E., et al. 2014. J. Biol. Chem.289, 10975.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany