1539296-45-1

PF470 (PF-06297470) is a negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5) with significant efficacy in Parkinson's disease models, but clinical development was halted due to potential issues found in toxicology studies.

PF-06297470 is a potent negative allosteric modulator of the Metabotropic Glutamate Receptor 5 (mGluR5). PF-06297470 binds to mGluR5 with a Ki of 0.9 nM. The compound PF-06297470 displays slight antagonism of mGluR1 (IC50 = 30.5 mM)with no agonist or antagonist activities against any other mGlu receptor subtype at concentrations up to 50 mM. PF-06297470 reduces dyskinesia in a rodent (MPTP)-rendered Parkinsonian model of L-DOPA-induced dyskinesia (PD-LID).

[1] Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator