Research Lines

Drug discovery for neurodegenerative diseases (Head: Ana Martínez)

Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system, the peripheral nervous system or both. There is no effective treatment for ND, and the drugs currently marketed are only palliative, symptom-oriented, albeit with several side effects. There is an urgent need in our society to discover and develop disease-modifiying agents for such pathologies including Alzheimer’s and Parkinson’s diseases and amyotrophic lateral sclerosis among others. Moreover, as increasing age is one of the major common risk factors to suffer a ND, the number of patients is increasing as the life-expectancy is risng every day. Patients, caregivers and health systems need effective drugs to stop such huge epidemy. Since 1996, our laboratory works intensively in that direction joining high level expertise in drug design and medicinal chemistry. Our long-term goal is to translate our new molecules into the discovery of novel therapeutics for the treatment and prevention of ND. Efforts in this direction include several of our drug candidates in on-going clinical trials for the treatment of different pathologies. Our strategy involves protein kinases as main targets to modulate neurodegeneration, such as GSK-3, CK-1, LRRK2 or TTBK1 and cAMP-specific phosphodiesterases such as PDE7 and PDE8. Moreover, as ND are very complex disorders, multitarget designed approach in drug discovery is other of our leading strategies.
Finally, we are also involved in “steamistry” a field that looks for modulating endogenous neurorepair mechanisms as new hippocampal neurogenesis with small molecules. 

Drug discovery for neglected tropical diseases (Head: Carmen Gil)

Neglected tropical diseases (NTDs) are a diverse group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries and affect more than one billion people. These diseases affect the world’s most vulnerable populations, almost exclusively poor and powerless people living in rural areas and urban slums of low-income countries.
The existing chemotherapy for these diseases like American trypanosomiasis (Chagas disease), human African tripanosomiasis (sleeping sickness), leishmaniasis or malaria among others, is less than satisfactory in terms of its lack of effectiveness, associated toxicity and also drug resistance. In the absence of vaccines, new chemotherapies are needed urgently to help in the prevention and control of these parasitic diseases.
We carry out the search for new drugs for NTDs using both target-based and phenotypic approaches. Phenotypic screening is a powerful method in both neglected and non-neglected diseases and has been successfully used. Identification of molecular targets from phenotypic approaches can be a way to identify potential new drug targets. Regarding target-based approach, we are focused on the development of parasite phosphodiesterase and kinase inhibitors as new drugs for the treatment of tropical diseases.

Chemoinformatics applied to drug discovery (Head: Nuria Campillo)

Drug discovery and development are still a challenging task for medicinal chemists. Chemoinformatics deals with the identification, development and optimization of efficient drugs by using computational techniques. Chemoinformatics tools help medicinal chemists to better understand complex structures of chemical compounds.
At present, it would be unimaginable to face a drug development program without applying appropriate chemoinformatics strategies. In recent years the focus on target affinity and activity has been complemented with techniques to address physico-chemical properties such as lipophilicity and solubility, biological properties such as absorption, distribution, metabolism, elimination and toxicity.
Our group applies both computational approaches (ligand-based and target-based) during hit identification and lead development process by using a great variety of computational tecniques as docking studies, virtual screening, molecular dynamics, QSAR studies etc.

Dynamic Combinatorial Chemistry in Biological Systems (PI: Ruth Pérez)

The development of synthetic molecules that mimic the precision of nature in molecular recognition represents a huge challenge to chemists. Dynamic combinatorial chemistry (DCC) holds enormous potential for drug discovery. In Dynamic Combinatorial Chemistry (DCC), building blocks react with one another using reversible chemical reactions giving mixtures of oligomers (Dynamic combinatorial libraries, DCLs). The composition of the DCLs after reaching equilibrium is determined by the relative stabilities of the different library members. If a target molecule is added to the system and one or more molecules show affinity to the target species, these compounds will, according to Le Chatelier’s principle, be amplified on the expense of the other non-bonding constituents. The identification of the best binders avoids the need for synthesis, purification and characterization of each library member, speeding the identification and optimization of novel ligands for biological targets.