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The Heart of Drug Discovery and Development: Rational Target SelectionSpector R.a · Vesell E.S.b
aRobert Wood Johnson Medical School, New Brunswick, N.J., and Harvard-MIT Program in the Health Sciences, Cambridge, Mass., and bDepartment of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pa., USA Corresponding Author
Elliot S. Vesell, M.D.
Department of Pharmacology, Pennsylvania State University College of Medicine
500 University Drive
Hershey, PA 17033 (USA)
Tel. +1 717 531 8285, Fax +1 717 531 5013, E-Mail firstname.lastname@example.org
Critical to the discovery and development of drugs and vaccines is the rational selection of biochemical, immunologic or molecular targets. To understand the rationale for target selection, we review strengths and weaknesses of the four main approaches: whole animal disease models; molecular targeting; epidemiology/observation studies, and genomics. After classifying diseases into those with a relatively stable pathophysiology (e.g., hypertension and gout) versus those with an unstable pathophysiology (e.g., AIDS and influenza) to aid in understanding target selection, we provide examples of successful and unsuccessful selection of drug and vaccine targets, focusing on the molecular and epidemiological/observational approaches. We discuss the reasons that molecular targeting has led to successful control of many diseases, whereas the epidemiological/observational approach has had a checkered history. We also assess the potential power of the genomic approach, specifically the curative versus controlling/preventive strategies. With combined genetic and molecular approaches and judicious use of whole animal models and properly performed epidemiology/observation studies to select the appropriate targets, the future for controlling, preventing and even curing many diseases is very bright indeed.
© 2006 S. Karger AG, Basel