ABSTRACT
A 1996 report projecting that the top 20 large pharma companies would each suffer a shortfall of 1.3 compounds was recently updated to reveal that the gap has increased to 2.3 compounds per company. This is despite the thousands of potential genomic-based targets that have been identified since. Clearly, if this is the case, the industry is facing a very serious challenge. Two major bottlenecks have been identified as contributing, viz., (i) target validation and (ii) diversity-oriented chemistry [which needs to be replaced by ‘‘target-oriented’’ chemistry (1)]. Unvalidated targets are deemed quite useless, and diversity-oriented chemistry has led to an unreasonable number of possible compounds thatmight be effective in disease therapy. The genomics revolution caused a paradigm shift from chemistry-based research toward informatics-basedprograms, but now the trend seems to focus oncharacterizing the target itself. If there is truly an evolutionary convergence of structures, it is
possible that these fundamental characteristics could lead to amultitude of biological effects. To follow this concept to its logical conclusion, companies are reconfiguring their approaches away from disease management towards target management. The postulate is that chemistry-oriented understanding of targets [such as G-protein coupled receptors (GPCRs) or kinases] would provide access to a greater number of therapeutic areas.
