A Perspective on the Evolution of Collaborative Drug Discovery and Future Challenges

Views about collaborative drug discovery changed from caution to advocacy in a few years. Milestones were the 2004 NIH Molecular Libraries Screening Center Network and library with screening data deposited to Pubchem; the 2008 Wellcome Trust transfer of proprietary chemogenomic data to the public; and in 2008, the formalization of collaborative efforts in the Clinical and Translational Science Pharmaceutical Assets Award portal. The biology/medicinal chemistry interface is difficult in academic drug discovery, with its wide range in academic drug discovery skills sets. Academics talk about innovation, thinking out of the box, maximum chemical diversity, and not being limited by preconceived rules and filters. Industry people talk about pragmatism, lessons learned, and about worthless screening compounds. Chemistry space errors impede academic drug discovery and collaborations. Screening diverse libraries is the worst way to discover a drug. Biologically active compounds occur in small tight clusters infrequently through chemistry space. Currently, well-known problematic functionality is replaced with more subtle problem compounds. Medicinal chemistry quality suffers when the academic choice is publish or perish. Hypothesis-driven research is a concern for future collaborative drug discovery because biology research driven by hypothesis can often be wrong. Complex natural products cannot be analyzed because the shapes are uncertain. This hinders exploitation of natural products in drug discovery and chemical biology.