Francisco Javier Luque Garriga
Universidade de Barcelona
Disclosing the molecular determinants of bioactive compounds: From chemical structure to mechanisms of drug action.
Drug design relies on the concept that a small molecule interacts with a physiological target in such a way that the strength of the interaction (affinity) is the main determinant of the therapeutic response. This assumption resides at the heart of structure-based drug design strategies, by which the chemical structure of a given compound with moderate but promising properties is subsequently modified in order to obtain a lead candidate.
Despite the efforts spent in developing a wide range of structure-based approaches and the integration within multidisciplinary research that combines molecular biology, biophysics, combinatorial chemistry, high-throughput screening and genomics, it is paradoxical that the number of chemical entities released along the last years has risen only slightly in spite of the substantial increase in development investment. This situation reflects our still limited understanding of the molecular determinants of drug activity and the complexity of biological systems.