VU6024578 (BI02982816) is a selective and CNS penetrant metabotropic glutamate receptor subtype 1 (mGlu1) positive allosteric modulator (PAM) with EC50 of 54 nM and 46 nM for human and rat mGlu1 respectively.
VU6024578 also maintains across species, with mouse (EC50 = 27 nM (89% Glumax) [n = 5] (pEC50 = 7.59 ± 0.07)) and dog (EC50 = 87 nM (129% Glumax) [n = 3] (pEC50 = 7.07 ± 0.07)) being in-line with human and rat mGlu1 PAM activity.
VU6024578 displays no agonism up to 30 μM for mGlu5, also is inactive at 5-HT2B, but a functional antagonist at the peripheral BZD (IC50 = 207 nM).
VU6024578 is active in both amphetamine-induced hyperlocomotion (minimum effective dose (MED) = 3 mg/kg, p.o.) and MK-801 induced disruptions of novel object recognition (minimum effective dose = 10 mg/kg p.o.).
VU6024578 is a best-in-class in vivo rodent tool compound to study selective mGlu1 activation.