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Everything Old is New Again: Phenotypic Screening

Phenotypic screening is once again popular at many large pharmaceutical companies, as the targeted drug discovery approach is being considered too limiting in certain ways, says Joanne Kotz at SciBX. "Phenotypic screens used to be the mainstay of drug development," Kotz says. Since the 1980s, advances in molecular biology and genomics have led drug companies to use targeted screening method to develop drugs. "Over the last decade, however, some drug developers have questioned whether an over-reliance on genetic approaches to validating targets for subsequent target-based drug discovery has resulted in reduced success in discovering first-in-class medicines," Kotz adds.

This topic was the focus of the recent Addressing the Challenges of Drug Discovery Keystone Symposium in Tahoe City, Calif. At a number of talks, researchers from academia and industry debated the various circumstances under which it might be advantageous to use a phenotypic screen instead of a targeted approach, Kotz says. Both have their pros and cons: On one hand, the biology of some diseases is poorly understood and a phenotypic screen is the best bet for finding a treatment, while, on the other hand, phenotypic screening can't tell a researcher if a drug is finding or hitting a target.

At In the Pipeline, Derek Lowe says he's been wondering "if the whole molecular-biology target-based approach has been something of a dead end." Recent analyses have shown that phenotypic screening is more productive for drug discovery, anyway, he adds, "and an overemphasis on individual targets has been suggested as a reason for the lack of productivity in drug discovery."

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