Defining the role of pharmacology in the emerging world of translational research.
Pharmacology is focused on studying the effects of endogenous agents and xenobiotics on tissue and organ function. Analysis of the concentration/response relationship is the foundation for these assessments as it provides quantifiable information on compound efficacy, potency, and, ultimately, side-effect liability and therapeutic index. Historically, pharmacology has been viewed as a unifying, hierarchically integrated, and technologically agnostic discipline. Besides being important in the development of new medications, pharmacological research has led to a better understanding of disease pathogenesis and progression. By defining the effects of compounds in vitro and in vivo, pharmacology has provided the means to validate, optimize, and advance new chemical entities (NCEs) to human testing. With the advent of molecular biology-based assay systems and a technology-driven (high-throughput screening, combinatorial chemistry, SNP mapping, systems biology) reductionistic focus, the integrated, hypothesis-driven pharmacological approach to drug discovery has been de-emphasized in recent years. This shift in research emphasis is now viewed by many as a major factor in the decline of new drug approvals and has led to various initiatives, the most notable being the Critical Path and Phase 0 clinical trial initiatives launched by the US Food and Drug Administration (FDA). These programs underscore the growing need for individuals trained in integrative pharmacology and having a background in molecular pharmacology to drive the drug discovery process and to fostering the translational research that is now considered vital for more rapidly identifying novel, more effective, and safer medications.
Department of Molecular and Integrative Physiology, Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.
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