Abstract

It has been estimated that the cost of bringing a new drug onto the market is 10 years and 0.5-2 billions of dollars, making it a non-profitable project, particularly in the case of low prevalence diseases. The advances in Systems Biology have been absolutely decisive for drug discovery, as iterative rounds of predictions made from in silico models followed by selected experimental validations have resulted in a substantial saving of time and investments. Many diseases have their origins in proteins that are not located in the cytosol but in intracellular compartments (i.e. mitochondria, lysosome, peroxisome and others) or cell membranes. In these cases, biocomputational approaches present limitations to their study. In the present work, we review them and propose new initiatives to advance towards a safer, more efficient and personalized pharmacology. This focus could be especially useful for drug discovery and the reposition of known drugs in rare and emergent diseases associated with compartmentalized proteins.

Keywords: Systems biology, diseasomes, compartmentalized proteins, drug discovery, rare diseases, lysosome, mitochondria, peroxisome.