Biomedical Engineering Reference
In-Depth Information
14
YEAST AS A MODEL IN
HIGH-THROUGHPUT SCREENING OF
SMALL-MOLECULE LIBRARIES
IRENE STEFANINI, CARLOTTA DE FILIPPO, AND DUCCIO CAVALIERI
14.1
INTRODUCTION
14.1.1 The Quest for Rapid and Smart Biological Assays
The pharmaceutical industry is facing a difficult period. The coincidence of pend-
ing patent expirations for major drug classes and a series of falling success rates in
the development of innovative therapeutics has affected the research and develop-
ment sectors significantly [1,2]. By chance or necessity, the gaining social impact
of specific diseases such as cancer and Alzheimer's, has obliged most companies to
investigate the same or similar targets and approaches [3]. Actually, the PubChem
[4] and ChemBank databases encompass nearly 57 and 2.5 million compounds,
respectively. Furthermore, synthetic chemistry has reached an unprecedented level
of sophistication and execution, allowing for the rapid, economically affordable, and
often parallelizable synthesis of a large plethora of molecules [5,6]. When studying a
molecule selected either for its role in the onset of a disease or as a suitable therapeutic
target, the availability of widespread chemical libraries represents a precious launch
pad for research on molecules able to modify the biological functions of the target.
During the past two decades, the “targetphilia” [7]—the target-based drug discovery
approach—allowed for the identification of novel lead compounds and therapeutic
candidates. Despite these promising results, the overall approval rate for new chem-
ical entities has maintained a flat trend [8]. Yet the targeted approach forbids the
