The discovery of first-in-class drugs: origins and evolution.
Nat Rev Drug Discov
; 13(8): 577-87, 2014 08.
Article
in En
| MEDLINE
| ID: mdl-25033734
ABSTRACT
Analysis of the origins of new drugs approved by the US Food and Drug Administration (FDA) from 1999 to 2008 suggested that phenotypic screening strategies had been more productive than target-based approaches in the discovery of first-in-class small-molecule drugs. However, given the relatively recent introduction of target-based approaches in the context of the long time frames of drug development, their full impact might not yet have become apparent. Here, we present an analysis of the origins of all 113 first-in-class drugs approved by the FDA from 1999 to 2013, which shows that the majority (78) were discovered through target-based approaches (45 small-molecule drugs and 33 biologics). In addition, of 33 drugs identified in the absence of a target hypothesis, 25 were found through a chemocentric approach in which compounds with known pharmacology served as the starting point, with only eight coming from what we define here as phenotypic screening testing a large number of compounds in a target-agnostic assay that monitors phenotypic changes. We also discuss the implications for drug discovery strategies, including viewing phenotypic screening as a novel discipline rather than as a neoclassical approach.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Discovery
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Rev Drug Discov
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2014
Type:
Article
Affiliation country:
Switzerland