VU6005649

2137047-43-7

C16H12F5N3O

10 mM in DMSO

GPCR/G Protein; Neuronal Signaling

VU6005649 is a CNS penetrant mGlu_7/8 receptor agonist with EC₅₀s of 0.65 uM and 2.6 uM for mGlu₇ receptor and mGlu₈ receptor, respectively. IC50 & Target: EC50: 0.65 uM (mGlu₇ receptor ), 2.6 uM (mGlu₈ receptor)^[1] In Vitro: VU6005649 is a CNS penetrant mGlu_7/8 receptor agonist with EC₅₀s of 0.65 uM and 2.6 uM for mGlu₇ receptor and mGlu₈ receptor, respectively. VU6005649 displays a terminal K_p of 2.43 with total brain levels ca.9x above the mGlu₇ positive allosteric modulator (PAM) in vitro EC₅₀^[1]. In Vivo: When VU6005649 (compound 9f) is dosed at 30 mg/kg IP in 10% Tween 80/H₂O (0.75 mg/kg. s.c. amphetamine), no efficacy is observed in this assay. VU6005649 shows modest but significant pro-cognitive effects on associative learning in wild-type mice and the first example of efficacy of an mGlu_7/8 positive allosteric modulator (PAM) in this model^[1].