In vitro activity: VU0357121 do not bind at the MPEP allosteric site of mGlu5, thus do not possess mGlu5 NAM activity. The A809V/rmGlu5 mutation inhibited the ability of VU0357121 to shift the glutamate concentration–response curve, whereas the response to VU0357121 is not altered by the F585I/rmGlu5 mutation. VU0357121 show weaker cooperativity in the Ca2+ mobilization assay in the low-expressing HEK293A-mGlu5 cell line.

Kinase Assay: VU0357121 is a novel positive and highly selective allosteric modulator (PAM) of mGlu5R with EC50 of 33 nM.

Cell Assay: VU0357121 is a novel and highly selective positive allosteric modulator (PAM) of mGlu5 (metabotropic glutamate receptor 4) with EC50 of 33 nM; it is inactive or very weakly antagonizing at other mGlu receptor subtypes. ositive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu4), including N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclinical models of PD. Mutagenesis studies indicate that VU0357121 and related analogues bind to a yet uncharacterized allosteric site on mGlu(5), distinct from CPPHA, yet share a functional interaction with the MPEP site.