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The discovery of first-in-class drugs: origins and evolution

Eder, Joerg, Sedrani, Richard and Wiesmann, Christian (2014) The discovery of first-in-class drugs: origins and evolution. Nature Reviews Drug Discovery, 13 (8). pp. 577-587. ISSN 1474-17761474-1784


Recent analyses claim phenotypic screening to be superior to target-based approaches for drug discovery. However, looking at the etiology and chronology of events that led to the approval of all 106 first-in-class drugs from 1999 to 2012, we realized that the majority of these (73) were discovered through target-based approaches. Of 31 drugs identified in the absence of a target hypothesis only 7 were found using true phenotypic screening. The discovery of the other 24 ‘phenotypic’ drugs occurred through a chemocentric approach where a particular compound with known pharmacology served as the starting point. We also found that the median time from first disclosure of the concept (target, pathway, chemotype) to FDA approval was 25 years for non-target-based and 20 years for target-based drugs. Few of the non-target based drugs had their origin after 1985, the time around which the technologies necessary for target-based approaches were established. We conclude that target-based drug discovery is successful, and recognize that HTS and other innovations applied in the past 25 years have only recently started to have a major impact on new approvals. We further suggest viewing phenotypic screening as a logical evolution of target-based approaches and consider it a novel discipline rather than a neoclassic approach, with all implications.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 04 Jul 2016 23:46


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