Principles of early drug discovery

Abstract

Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12–15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.

2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains

“…Nevertheless, potential drug−drug interactions were evaluated using human CYP450 inhibition studies. Compounds 5e, 5m, and 5s did not show any significant inhibition (IC 50 value < 10 μM) 21 to the evaluated liver enzymes, denoting a minimal risk of metabolic drug−drug interactions. Finally, the most active compounds 5e, 5m, and 5s were subjected to potential cardiac toxicity evaluation in a zebrafish (Danio rerio) model.…”

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

“…Drug discovery is typically a long and very expensive process, requiring an average of 10 to 20 years and an investment of more than $1.0 billion before a new compound with activity against a specifi c target is identifi ed, characterized, and developed for clinical applications (25) (26) . In the case of leishmaniasis, there are few new antileishmanial drugs in the pipeline, and drug resistance is increasing.…”

Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective

“…Although some of the more general considerations involved in target selection are discussed here, several recent publications are available that provide additional rationale for target selection under specific circumstances [3][4][5][6][7][8][9][10] .…”