Main Research Lines
Resistance to antitumorals targeting tubulin is possible through three different mechanisms
Overexpression of drug efflux membrane pumps
Mutations in the ligand binding site.
Overexpression of tubulin isotypes less sensitive to the drug employed.
Our working lines are focused on:
- An understanding of the cellular, biochemical and structural mechanisms required for drugs to overcome the three known mechanisms of resistance against tubulin targeting compounds, this implies the use of biophysical, structural (Figure 2) and cell biology techniques, not excluding in vivo studies if needed.
- The design, synthesis and biochemical and biological evaluation of new compounds with the capacity to overcome resistance against tubulin targeting drugs, including drugs with a covalent mechanism of action as those based in the Zampanolide and Cyclostreptin chemotypes (Figure 3) characterized by our group.
- The development of tools to seek other compounds targeting new binding sites in tubulin.
- The design and evaluation of a model Aspergillus nidulans system and tumoural cell cutures in which drugs active against mutant tubulins or altered isotype expression systems can be evaluated and mutant tubulins engineered.