Phenotype Reigns Supreme

A new article in Nature Reviews Drug Discovery shows that phenotypic screening accounts for a large number of drug approvals, says In the Pipeline's Derek Lowe. The paper's authors looked back at 259 drugs — 75 first-in-class, 164 followers, and 20 imaging agents — approved between 1999 and 2008, and found that 100 were discovered using a target-based approach and 58 through phenotypic approaches, Lowe says. Of the 75 first-in-class drugs, 28 were assigned to phenotypic assays and only 17 to target-based approaches. "CNS and infectious disease were the therapeutic areas that benefited the most from phenotypic screening, which makes sense. We really don't understand the targets and mechanisms in the former, and the latter provide what are probably the most straightforward and meaningful phenotypic assays in the whole business," Lowe says. The paper's authors concluded that while research on drugs has increasingly focused on targets, this has come at the expense of preclinical assays that "translate more effectively into clinical effects in patients with a specific disease." Lowe agrees, adding, "Will we look back on the late 20^th century/early 21^st as a target-based detour in drug discovery?"