BioCentury
ARTICLE | Strategy

Rethinking mechanisms of drug discovery

July 14, 2011 7:00 AM UTC

A Roche team has concluded that overreliance on simplistic, target-centered screens early in drug development may inadvertently select for compounds destined to fail in late-stage trials.1 The resulting high attrition rates and low R&D productivity could be reversed, the researchers believe, by refocusing discovery strategies on phenotypic screens that account for complex mechanisms of action and cell signaling pathways.

"Late-stage drug failures involving, for example, poor bioavailability or off-target toxicity may ultimately derive from a preclinical optimization process that considered the target in an overly simplified setting-as typified, for example, by the classic in vitro binding assay, which doesn't enable optimization of the therapeutic index," corresponding author David Swinney told SciBX...