Figure 5.
mGlu1 NAM activity of certain NAMs is dependent on residue 757 in a calcium mobilization assay using cells expressing rat (closed triangles) and human (closed circles) WT mGlu1 and rat V757L (open triangles) and human L757V (open circles) mGlu1. (a) A large decrease in potency is observed at rmGlu1 V757L compared to WT for BAY36-7620 which is rescued by hmGlu1 L757V. (b) A complete loss of activity is observed at rmGlu1 V757L compared to WT for VU0410425. The hmGlu1 L757V mutant restores activity to levels similar to those seen for rmGlu1 WT. (c) A small decrease in potency is observed for DFMTI at rmGlu1 V757L (21 nM) compared to WT (8 nM). The hmGlu1 L757V mutant restores activity to levels similar to those seen for rmGlu1 WT.