Rapid advances in biomedical sciences in recent years have drastically accelerated the discovery of the molecular basis of human diseases. The great challenge is how to translate the newly acquired knowledge into new medicine for disease prevention and treatment. Drug discovery is a long and expensive process, and the pharmaceutical industry has not been very successful at it, despite its enormous resources and spending on the process. It is increasingly realized that academic biomedical research institutions ought to be engaged in early-stage drug discovery, especially when it can be coupled to their basic research. To leverage the productivity of new-drug development, a substantial acceleration in validation of new therapeutic targets is required, which would require small molecules that can precisely control target functions in complex biological systems in a temporal and dose-dependent manner. In this review, we describe a process of integration of small-molecule discovery and chemistry in academic biomedical research that will ideally bring together the elements of innovative approaches to new molecular targets, existing basic and clinical research, screening infrastructure, and synthetic and medicinal chemistry to follow up on small-molecule hits. Such integration of multidisciplinary resources and expertise will enable academic investigators to discover novel small molecules that are expected to facilitate their efforts in both mechanistic research and new-drug target validation. More broadly academic drug discovery should contribute new entities to therapy for intractable human diseases, especially for orphan diseases, and hopefully stimulate and synergize with the commercial sector.
2010 Mount Sinai School of Medicine.