Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines

David C. Swinney

Clinical Pharmacology & Therapeutics · 2013 · 412 citations · 4 references

Concepts

TL;DR

Drug discovery uses both target‑based, hypothesis‑driven approaches and phenotypic, empirical methods that rely on observable responses. Phenotypic methods proved more successful than target‑based strategies for first‑in‑class small‑molecule drugs, largely because they uncover the molecular mechanism of action without prior bias.

Abstract

Current drug discovery strategies include both molecular and empirical approaches. The molecular approaches are predominantly hypothesis-driven and are referred to as target-based. The empirical approaches are referred to as phenotypic because they rely on phenotypic measures of response. A recent analysis revealed the phenotypic approaches to be the more successful strategy for small-molecule, first-in-class medicines. The rationalization for this success was the unbiased identification of the molecular mechanism of action (MMOA).

References

4