4 Drug Discovery: Design

and Serendipity

Ronald R. CobbandLeslie J. Molony

4.1 Introduction

How is it that medicines are discovered? In ancient
times, and even today, tribal people knew the heal-
ing or hallucinogenic properties of indigenous
plants and animals. The knowledge was accumu-
lated through generations, recorded by chant and
living memory and was derived largely from
human experience. Although many of the drugs
in use today were discovered by chance, most
drug discovery scientists engage in directed
research, based on a series of steps, each requiring
substantial scientific input. Although available
facilities, resources, technology focus or even cor-
porate culture can define the procedures followed
by researchers at particular institutions, there are
some obvious, generally applicable milestones in
this process that facilitate the discovery of thera-
peutics.

Targeted medicines and their
implications

The understanding and use of medicines by physi-
ciansandhealershaveevolvedsignificantly,keeping
in step with technological and biological break-
throughs. From the use of herbal remedies to toxic

chemotherapeuticsubstances(Vincaalkaloidsbeing

anexampleofboth!),today’sidealcaseisamedicine

directed atanidentifiedpathologicalprocess, and/or

specific receptors controlling these pathologies.

Well-targeted medicines are often substantially

safer, and are likely to have fewer adverse events

(sideeffects)inalargerpatientpopulationthanthose

with multiple pharmacological properties.

Research and development leading to a new,

well-targeted pharmaceutical product is a long,

complex and expensive process. Historically, the

cost of a new drug has been escalating by close to

$100M every five years. In 2005, the estimated cost

to bring a new drug from the laboratory bench into

the marketplacewas US$800 millions (abouts 670

millions or £450 millions).Averagedevelopment

time is 7–10 years, although some ‘blockbuster’

drugs have taken 20 years. In the universe, of all

commercial products, these are among the longest

of all development cycles, permitting patent

exploitation among the shortest periods.

Hence, the drug discovery and development

process is a two-part exercise in mitigating the

economic punishment to product sponsors while

maximizing the probability that something that can

bedeveloped successfullyis actually found.Asfew

as 1% of promising lead molecules will be tested in

human beings; fewer than one-third of those tested

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier
#2007 John Wiley & Sons, Ltd ISBN: 978-0-470-09313-9