Drug Discovery


DRUG DISCOVERY cutting-edge technologies meet traditional paradigms in assay development


With more than 1,500 drugs approved by the Food and Drug Administration (FDA) on the market, the easiest disease targets are already covered1. Today’s scientists are challenged to find new compounds, acting alone or in combination, on intractable targets to treat multicausal diseases including cancers, metabolic and psychiatric disorders. The technologies and assays coming to the market enable new avenues in drug discovery creating opportunities to study complex disease mechanisms and find cures for the indications mentioned above.


F


THE FUTURE OF


rom the ancient Egypt Pharmacopeia described in Ebers Papyrus until the emer- gence of high throughput screening (HTS) in


the early 1990s, drug discoveries mostly resulted from serendipity, intuition and trial-and-error efforts (forward pharmacology) or from first-gen- eration rational drug design (reverse pharmacolo- gy). The discovery of penicillin from mould secre- tions reported by Fleming originated from serendipity and intuition2. The H2 blocker and antacid cimetidine (Tagamet), derived from his- tamine which is known to promote gastric acid release, is a representative example of a drug devel- oped using reverse pharmacology3.


Drug Discovery World Fall 2018


The traditional drug discovery approaches used


until the end of the 1980s revealed too time-con- suming, low-throughput and cost-ineffective by the industry which – relying on automation and sec- ond-generation (computer-assisted) rational drug design – started to perform high-throughput screening campaigns of large combichem libraries on purified biological targets. Despite the increas- ing complexity of the disease targets to address, HTS campaigns contributed to deliver close to 50% of the total drugs approved by the FDA since 1930 (Figure 1)1. However, the drug attrition rate observed during clinical trials remains high in all therapeutic areas mainly due to a lack of efficacy


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By Dr Roger Bossé


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