Abstract

How many times have you read a research article that ends with the conclusion that a particular research finding has the potential to lead to a new therapeutic? Given the tremendous interest in translational research and the increase in pharmaceutical research spending, why are fewer new chemical entities being approved each year? In an informal survey of academic and industrial scientists, many different explanations were proposed: the easy targets are gone; industry places too much emphasis on 'me too' drugs; preclinical and clinical safety testing are filtering out more compounds on the basis of weakly predictive assays; too much effort is being wasted on targets that are putatively validated by molecular and cellular biology but that ultimately have unknown consequences on an organismal level; and the drug discovery process has become too formulaic and compartmentalized to allow for “inspired insights” from scientists who were formerly imbedded in all aspects of a project. Given these and other problems, it is worthwhile to consider both new and established approaches that can stimulate the discovery and development of new drugs.