The Translational medicinal and biological chemistry group led by Prof. Ana Martinez is placed at the Biological Research Center (CIB-CSIC). It is a multidisciplinary team combining scientists with different backgrounds (chemistry, pharmacy and biology). The group is focused on the design, synthesis, biological evaluation, study and further optimization of pharmacokinetic properties of structurally diverse chemical entities for drug discovery. The efforts of the group are focused on the discovery of innovative drugs with novel mechanism of action as disease-modifying agents for unmet severe pathologies such as neurodegenerative diseases.

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 bearing different pharmacophore moieties in the same molecule to interact with different targets, and improving ADME properties of the candidates, among others.

Our research is applied with a high content of translational research. The group's research programs are designed from the early stages of drug discovery to proof of efficacy in representative animal models. Scientific collaborations and technology transfer to companies in the pharmaceutical sector are key tasks in achieving our goals.

 

Members:

Ana Martínez Gil, Research Professor CSIC. PhD in Chemistry

Carmen Gil Ayuso-Gontán, Research Scientist CSIC. PhD in Pharmacy


Nuria Campillo Martín, Tenured Scientist CSIC. PhD in Chemistry 


Valle Palomo Ruiz, Research Associate. PhD in Chemistry

Elisa Rojas Prats, PhD student. BSc Chemistry

Vanesa Nozal, PhD student. BSc Chemistry

Loreto Martínez González, PhD student. BSc Biology

Selected publications

 

­ Design and study of innovative drugs for ALS and other neuromuscular diseases:

Salado, I. G.; Redondo, M.; Bello, M. L.; Perez, C.; Liachko, N. F.; Kraemer, B. C.; Miguel, L.; Lecourtois, M.; Gil, C.; Martinez, A.; Perez, D. I. Protein kinase CK-1 inhibitors as new potential drugs for Amyotrophic Lateral Sclerosis.  J. Med. Chem. 2014, 57, 2755­2772.

Alquézar, C.; Salado, I. G.; de la Encarnación, A.; Pérez, D. I.; Moreno, F.; Gil, C.; López de Munain, A.; Martínez, A.; Martín-Requero, A. Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: a novel strategy for the treatment of frontotemporal dementia. Mol. Neurodegener., 2016, 11:36.

de Munck García, E.; Palomo, V.; Muñoz-Sáez, E.; Perez, D. I.; Gómez Miguel, B.; Solas, M. T.; Gil, C.; Martinez, A.; Arahuetes Portero, R. M. Small GSK-3 inhibitor shows efficacy in a motor neuron disease murine model modulating autophagy. PLoS One., 2016, 11, e0162723.

Palomo, V.; Perez, D. I.; Roca, C.; Anderson, C.; Rodriguez-Muela, N.; Perez, C.; Morales-Garcia, J. A.; Reyes, J. A.; Campillo, N. E.; Perez-Castillo, A. M.; Rubin, L. L.; Timchenko, L. T.; Gil, C.; Martinez, A. Subtly modulating Glycogen Synthase Kinase 3 beta: allosteric inhibitors development and their potential for the treatment of chronic diseases. J. Med. Chem. 2017, 60, 4983­5001.

 

- Recent reviews in the field of innovative drugs for ALS:

Palomo, V.; Martinez, A. Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015). Exp. Opin. Ther. Patents, 2017, 27, 657­666.

Martinez, A.; Palomo, V.; Perez, D.I.; Gil, C. Drugs in clinical development for the treatment of amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs, 2017, 26, 403­414.

 

­ Search for clinical biomarkers of disease progression:

González-Muñoz, M.; Rodríguez-Mahillo, A. I.; Gil, C.; Morán, Y.; Moneo, I.; Martínez, A.; Mora, J. S. Glycogen synthase kinase-3β expression and phosphorylation in peripheral blood mononuclear cells of patients with Amyotrophic Lateral Sclerosis Br. J. Med. Med. Res., 2014, 4, 263­ 271.

 

­ Sporadic ALS animal model:

De Munck, E.; Muñoz-Sáez, E.; Miguel, B. G.; Solas, M. T.; Ojeda, I.; Martinez, A.; Gil, C.; Arahuetes, R. M. “β–N-methylamino-L-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): The first step towards an experimental model for sporadic ALS. Environ. Toxicol. Pharmacol. 2013, 36, 243­255.

de Munck, E.; Muñoz-Saez, E.; Miguel, B. G.; Solas, M. T.; Martinez, A.; Arahuetes, R. M. Morphometric and neurochemical alterations found in l-BMAA treated rats. Environ. Toxicol. Pharmacol. 2015, 39, 1232-1245.

Muñoz-Saez, E.; de Munck Garcia, E.; Arahuetes Portero, R. M.; Martinez, A.; Solas Alados, M. T.; Miguel, B. G. Analysis of beta-N-methylamino-L-alanine (L-BMAA) neurotoxicity in rat cerebellum. Neurotoxicology 2015, 48, 192-
   

 

 

CONTACTO:


 


 

 Coordinadora:

Ana Martínez (This email address is being protected from spambots. You need JavaScript enabled to view it.)

Gestora del Proyecto:

Nuria Mª Rivas (This email address is being protected from spambots. You need JavaScript enabled to view it.)

Centro de Investigaciones Biológicas (CIB-CSIC)

C/Ramiro de Maeztu, 9

28006 MADRID

 

 

 

 

 

 

             Proyecto ELA-MADRID.B2017/BMD-3813

 

 Proyecto financiado por la Comunidad de Madrid y la Unión Europea