Advances in genetics, biology, chemical synthesis and computational methods have contributed to the understanding of diseases and drugs and with all of the above, there is an expectation that we are in a better position than ever before to create effective medicines for our needs. The reality is, however, disconnected from the expectation - US FDA drug approval statistics show that the number of approved drugs, especially the first-in-class drugs, is not commensurate with our improved knowledge. In this perspective, we offer our views on the possible reasons for this, focusing on small-molecule drugs and suggest some ideas for further considerations.
Keywords: high-throughput screening; pan assay interference compounds (PAINS); polypharmacology; target-based screening; toxicophores.