Mechanism of action: Negative allosteric modulator of human mGluR5d, human mGluR5b

Preclinical pharmacology

AZ12977847 is a negative allosteric modulator of human mGluR5d, human mGluR5b, canine mGluR5c and rat mGluR5 with IC50 41, 20, 41 and 54nM respectively in vitro. AZ12977847 demonstrated IC50 values >25µM at other mGluR homologues (mGluR1-4 and mGluR6-8). AZ12977847 was shown to have limited CNS exposure in rats and so is thought to be restricted to the periphery. In oesophagostomised dogs, AZ12977847 achieved 50% inhibition of transient lower oesophageal sphincter relaxations at plasma compound exposures of approximately 1.5µM (unbound 0.18µM). Similar results were seen in ferrets.

Safety and tolerability

AZ12977847 was well tolerated in 7 day rat toxicology studies.

Additional Information

Gene information from the NCBi

This compound works on the following genes: