1428630-85-6

1428630-85-6 structure

Name: VU 0424465
Chemical Name: VU0424465
CAS Number: 1428630-85-6
Molecular Formula: C₁₉H₁₉FN₂O₂
Molecular Weight: 326.36
Catalog: Signaling Pathways Cell Cycle/DNA Damage PERK
Create Date: 2021-01-09 18:01:27
Modify Date: 2024-04-05 16:48:00
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].

Name	VU0424465
Synonyms	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

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.