VU 0424465

Names

[ Name ]:
VU 0424465

[Synonym ]:
5-[(3-Fluorophenyl)ethynyl]-N-[(2R)-3-hydroxy-3-methyl-2-butanyl]-2-pyridinecarboxamide
2-Pyridinecarboxamide, 5-[2-(3-fluorophenyl)ethynyl]-N-[(1R)-2-hydroxy-1,2-dimethylpropyl]-
VU0424465

Biological Activity

[Description]:

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 Ki value of 11.8 nM. VU0424465 is also a agonist for pERK1/2 in cortical neurons[1][2].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mGluR

Signaling Pathways >> Cell Cycle/DNA Damage >> PERK

Research Areas >> Neurological Disease

[Target]

mGlu5

[In Vitro]

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].

[References]

[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.

[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.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
533.8±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₉H₁₉FN₂O₂

[ Molecular Weight ]:
326.36

[ Flash Point ]:
276.7±30.1 °C

[ Exact Mass ]:
326.143066

[ LogP ]:
2.95

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.594

Related Compounds

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