Off BACE
Pfizer’s approach to defining inhibitor selectivity
With November’s Phase III failure of Eli Lilly and Co.’s (NYSE:LLY) β-amyloid inhibitor solanezumab for Alzheimer’s disease, and the pharma’s announcement last week that it was abandoning efforts to submit the compound for regulatory approval, eyes are turning upstream of amyloid plaques to inhibition of BACE, the enzyme that generates β-amyloid. In October, scientists at Pfizer Inc. (NYSE:PFE) described a chemoproteomic approach for defining the selectivity of BACE inhibitors that could help the field avoid the off-target retinal toxicity that has sidelined several programs.
Moreover, the company thinks the method can be applied broadly to more accurately test the specificity of compounds against a wide variety of targets...