VU0424465 

VU0424465 is a potent and partial PAM (positive allosteric modulator)-agonist for mGlu₅ mediated iCa²⁺ mobilization. VU0424465 exhibits high affinity at MPEP allosteric binding site, with a K_i value of 11.8 nM. VU0424465 is also a agonist for pERK1/2 in cortical neurons^[1][2].

VU0424465 exhibits robust agonist activity and induces calcium mobilization in the absence of glutamate (EC₅₀ = 171 ± 15 nM, maximum efficacy 65% compared to glutamate)^[2].
VU0424465 potentiates glutamate-induced calcium mobilization, with EC₅₀ of 1.5 ± 0.8 nM^[2].
VU0424465 shows significant bias away from iCa²⁺ mobilization and toward IP₁ accumulation (110-fold) and ERK1/2 phosphorylation (9-fold) in HEK293A-mGlu5-low cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

326.36

C₁₉H₁₉FN₂O₂

1428630-85-6

O=C(N[C@H](C)C(O)(C)C)C1=NC=C(C=C1)C#CC2=CC=CC(F)=C2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sengmany K, et al. Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery. Neuropharmacology. 2017;115:60-72.  [Content Brief]

  [2]. Rook JM, Noetzel MJ, Pouliot WA, et al. Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry. 2013;73(6):501-509.  [Content Brief]