Discovery research experiments

Stahl, M., Cuba, W. and Kansy, M. (2006) Integrating molecular design resources within modern drug discovery research the Roche experience. Drug Discovery Today, 11, 326-333. 

Completed drug discovery research studies indicate that a compound, or class of compounds, mediates a disease process and has potential as human therapeutic agent. Is this lead compound now ready to be transferred from the discovery area to a preclinical development group Should additional, nondefinitive experiments be conducted to characterize more fully the properties of the lead candidate If more studies are considered necessary, what experiments should be done ... 

This section describes some of the biological research experiments that could, and in most cases should, be conducted to evaluate the potential of a lead compound to become a developmental candidate. Figure 3 shows where these developability experiments fit into the drug discovery and development process. These nondefinitive developability studies may also uncover problems that have to be resolved before the definitive preclinical development studies required to support an IND submission are started and before the clinical protocols to evaluate the safety and efficacy of the drug candidate in humans are designed. 

Profile The company is an international provider of chemical tools for drug discovery and development. With main offices in San Diego, California, it also has a research, development, and production infrastructure in Russia. Members of ChemBridge s management team have senior executive and senior research experience with leading U.S., European, and Japanese pharmaceutical and biotech companies. 

Thus, a second key strategy in drug discovery is to improve the planning and interpretation of discovery experiments using pharmaceutical-profiling property data. Drug-discovery researchers of all disciplines should have access to compound property data and be aware of the potential effects on the experiments they are performing. 

Figure 15.2 illustrates some of the discovery bioactivity experiments in which a test compound must be successful to advance. If erroneous activity or selectivity data are generated or misinterpreted, the SAR will mislead the project team. SAR is a central strategy of drug-discovery research. If the activity assays are affected by properties in addition to target protein interaction, then the SAR will be a composite of multiple variables. Table 15.1 lists some of the potential effects on SAR from lack of property data application in planning and interpretation of drug-discovery bioassays. 

As discovery research moves forward, great value is derived from dosing experiments with living animals. In vitro profiling assays are used to predict the in vivo ADME performance, in order to select compounds for animal studies. 

This author recommends that sponsors consider using the CTD-recommended order of presentation for quality, nonclinical, and clinical results as a generic template for the definition of a drug development logic plan (as described in Chap. 1). The results from drug discovery efforts, preclinical research experiments, and earlier CMC evaluations can... 

Patent coordinators jobs are few and may be hard to find. They are not entry-level posts, but require direct experience of the work, for which employers seek B.S., M.S., or Ph.D. chemists. A qualified Ph.D. scientist achieves as a prerequisite the research successes that lead to patent applications. For a medicinal chemist employed in discovery research these successes are a series of biologically potent new compounds. For his counterpart in develop-... 

These scientists qualifications surpass what M.S. chemists offer. In summary, doctorate-level chemists demonstrate mastery of organic chemistry and proficiency in synthesis if they find employment in drug discovery or development research. Their dissertations present substantial pieces of original and successful research. Scientific publications, patent inventorships, and postdoctoral research experiences represent bonuses to any employer. 

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