VU 0409106

VU0409106 is a potent and selective mGlu5 negative allosteric modulator (NAM) with an IC50 of 24 nM. VU0409106 shows anxiolytic effects in rat models in a concentration-dependent manner. VU0409106 also penetrates the blood-brain barrier (BBB)[1][2].

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

mGlu5:24 nM (IC50)

VU0409106 (10 mg/kg; i.p.; once) penetrates the blood-brain barrier (BBB) and demonstrates good brain to plasma ratio that near unity[1]. Animal Model: CD-1 mice[1] Dosage: 10 mg/kg (10% Tween 80 formulation) Administration: Intraperitoneal injection. Result: 1.19Pharmacokinetic Parameters of VU0409106 in CD-1 mice[1]. IP (10 mg/kg) Plasma Tmax (h) 0.25 Plasma Cmax (ng/mL) 1450 Brain Tmax (h) 0.25 Brain Cmax (ng/mL) 1350 AUCplasma (ng/mL•h) 702 AUCbrain (ng/mL•h) 696 B/P ratio 0.99

[1]. Felts AS, et al. Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5779-85.

[2]. Morrison RD, et al. The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5. Drug Metab Dispos. 2012 Sep;40(9):1834-45.