HOME

         

El contenido de esta página requiere una versión más reciente de Adobe Flash Player.

Obtener Adobe Flash Player



All the research carried out at the Instituto de Quimica Medica is focused on the design, synthesis, study and further optimization of structurally diverse chemical entities for drug discovery. The efforts of our group are focused on the pharmacological validation of new targets for neurodegenerative diseases which will allow the discovery of innovative drugs with novel mechanism of action as disease-modifying agents for these unmet severe pathologies applying several techniques and methodologies of medicinal chemistry.

The research interests of our group are based on the discovery of new drugs able to promote neuroregeneration by

endogenous stimulation of the brain neurogenesis. We believed that this may represent an innovative way to find disease modifying agents for neurodegenerative pathologies such as Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS) or even multiple sclerosis, all of them characterized by a loss of neurons in particular regions of the nervous system.

Targets involved in neurogenesis are huge and most of them remain to be determined. For that reason, we have focused initially our projects and resources on four different targets with different degree of knowledge about their involvement in neurogenesis and axonal growth. We have chosen glycogen synthase kinase 3 (GSK-3), protein kinase CK1 (CK1), phosphodiesterase 7 (PDE7) and the nicotinic receptor (α4ß2 and α7) as potential neurogenic targets. All of these pharmacological receptors are involved in the pathology of neurodegenerative diseases and some of them may exert neuroprotective actions through antioxidant, anti-inflammatory and anti-excitotoxic properties.

For the design of our drugs (mainly small heterocyclic molecules with MW<500), different strategies will be used. These include computer-aided drug design, multifunctional compounds (DML's) bearing different pharmacophore moieties in the same molecule to interact with different targets, and improving ADME properties of the candidates, among others. Our own chemical library containing hundreds of compounds with privileged scaffolds will be also used in directed biological screening programs.

In 1996 we started our research on Alzheimer's disease therapy. Since then, we have discovered diverse chemical families of compounds that target glycogen synthase kinase 3 (GSK-3) or the peripheral site of acetylcholinesterase (AChE). Both families of compounds were transferred to a biotechnological company and two candidates called NP-12 and NP-61, respectively, are on clinical trials as disease- modifying drugs for Alzheimer's disease.