VU 0424465

Biological Activity

VU 0424465 is a potent mGlu₅ positive allosteric modulator (EC₅₀ = 1.5 nM) and agonist (EC₅₀ = 171 nM; maximum effect is 65% that of glutamate). Binds allosteric site with high affinity (K_i = 11.8 nM). Increases maximum response to glutamate by 30%. Exhibits bias towards signaling via IP₁ and ERK1/2 over iCa²⁺ in HEK293 and neuronal cells, and activates G_s in HEK 293 cells. Induces epileptiform activity in CA3 hippocampal neurons in vitro and convulsions in vivo.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity.
   Rook et al.
   Biol.Psychiatry., 2013;73:501
2. Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery.
   Sengmany et al.
   Neuropharmacology, 2017;115:60
3. Direct coupling of detergent purified human mGlu₅ receptor to the heterotrimeric G proteins Gq and Gs.
   Nasrallah et al.
   Sci.Rep., 2018;8:4407

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