Therapeutic area screening methods

Pfizer s search for new treatments spans hundreds of research projects across multiple therapeutic areas—more than any other company. Our scientists, clinicians, technicians, and other professionals employ state-of-the-art tools ranging from robotic high-throughput screening (a method pioneered by Pfizer) to sophisticated genomic studies, to deliver a steady stream ofinnovative new products that enhance human and animal health. 

In the past few years, LC-MS has rapidly conquered the clinical laboratory, and further developments in this area are expected for the near future. Recent reviews [2-3] highhghted the importance of such developments. Application areas for LC-MS in the clinical laboratory are therapeutic drag monitoring, neonatal screening, reference methods, and toxicology. Today, one should add the rapidly developing area of clinical biomarker discovery to this list [4] (Ch. 18.6). 

Development of therapeutic radiopharmaceuticals is one of the areas most widely explored by researchers. The many significant advances in this field have solved many of the technical problems involved in labelling biomolecules with a variety of radionuclides. These studies have the potential to provide a large array of target specific therapeutic radiopharmaceuticals [1.17]. However, to assist in the identification of an ideal agent, rehable laboratory methods for screening the potential candidates are essential. 

In this chapter, we have developed predictive models based on two well es-tabhshed methods (1) hierarchical quantitative structure-activity (HiQSAR) modeling, and (2) quantitative molecular similarity analysis (QMSA). We have reviewed published work in both of the above areas for important classes of heterocyclic compounds that have therapeutic and toxic effects. Predictive models can be developed based on experimental properties, substituent constants derived from such properties, and also theoretical descriptors which can be calculated directly from molecular structure, hi view of the fact that most potential therapeutic agents and the majority of known drugs and toxicants do not have experimental data available for their evaluation, theoretical descriptors are very useful in the initial screening of compound libraries. 

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