Group Leader/s

 

intro

The Translational medicinal and biological chemistry 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 our 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 and infectious diseases. Our group applies medicinal chemistry programs combining classical and computational medicinal chemistry.

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. The group has developed an in-house chemical library (called MBC library) containing over 1200 compounds with privileged scaffolds which is continuously growing and extensively used in our directed biological and computational screening programs.

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.

We are members of different national and international excellent research networks and infrastructures such as EU-OPENSCREEN (https://www.eu-openscreen.eu/) and CIBERNED (https://ciberned.es/). Furthermore, we have found two spin-offs focused on drug discovery and development: AnkarPharma and AItenea biotech.

Logos

 

 

Rojas-Prats, E.; Martinez-Gonzalez, L.; Gonzalo-Consuegra, C.; Liachko, N. F.; Perez, C.; Ramírez, D.; Kraemer, B. C.; Martin-Requero, Á.; Perez, D. I.; Gil, C.; de Lago, E.; Martinez, A.  [2020]. Targeting nuclear protein TDP-43 by cell division cycle kinase 7 inhibitors: A new therapeutic approach for amyotrophic lateral sclerosis. Eur J Med Chem 2020, doi: 10.1016/j.ejmech.2020.112968

Canal-Martín, A.; Pérez-Fernández, R.  [2020]. Protein-directed dynamic combinatorial chemistry: An efficient strategy in drug design. ACS Omega 2020, 5, 26307-26315

Vaca, G.; Martínez-González, L.; Fernández, A.; Rojas-Prats, E.; Porras, G.; Cuevas, E. P.; Gil, C.; Martinez, A.; Martin-Requero, A.  [2020]. Therapeutic potential of novel Cell Division Cycle Kinase 7 inhibitors on TDP-43-related pathogenesis such as Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS). J Neurochem 2020, doi: 10.1111/jnc.15118

Palomo, V.; Nozal, V.; Rojas-Prats, E.; Gil, C.; Martinez, A.  [2020]. Protein kinase inhibitors for Amyotrophic Lateral Sclerosis therapy. Br J Pharmacol 2020, doi: 10.1111/bph.15221

Castro-Sánchez, S.; Zaldivar-Diez, J.; Luengo, E.; López, M. G.; Gil, C.; Martínez, A.; Lastres-Becker, I.  [2020]. Cognitive enhancement, tau phosphorylation reduction and neuronal protection by the treatment of a LRRK2 inhibitor in a tauopathy mouse model. Neurobiol. Aging 2020, 96, 148-154.

Zaldivar-Diez, J.; Li, L.; Garcia, A. M.; Zhao, W.-N.; Medina-Menendez, C.; Haggarty, S. J.; Gil, C.; Morales, A. V.; Martínez, A.  [2020]. Benzothiazole-based LRRK2 inhibitors as Wnt enhancers and promoters of oligodendrocytic fate. J. Med. Chem. 2020, 63, 2638-2655.

Gil, C.; Ginex, T.; Maestro, I.; Nozal, V.; Barrado-Gil, L.; Cuesta-Geijo, M. A.; Urquiza, J.; Ramirez, D.; Alonso, C.; Campillo, N. E.; Martinez, A.  [2020]. COVID-19: Drug targets and potential treatments. J Med Chem 2020, 63, 12359-12386.

Martinez-Gonzalez, L.; Rodríguez-Cueto, C.; Cabezudo, D.; Bartolome, F.; Andrés-Benito, P.; Ferrer, I.; Gil, C.; Martin-Requero, A.; Fernández-Ruiz, J.; Martinez, A.; de Lago, E.  [2020]. Motor neuron preservation and decrease of in vivo TDP-43 phosphorylation by protein CK-1δ kinase inhibitor treatment. Sci. Rep. 2020, 10, 4449.

Maestro, I.; Boya, P.; Martinez, A.  [2020]. Serum- and glucocorticoid-induced kinase 1, a new therapeutic target for autophagy modulation in chronic diseases. Expert Opin Ther Targets 2020, 24 (3), 231-243.

Peřinová, R.; Maafi, N.; Korábečný, J.; Kohelová, E.; De Simone, A.; Al Mamun, A.; Hulcová, D.; Marková, J.; Kučera, T.; Jun, D.; Šafratová, M.; Maříková, J.; Andrisano, V.; Jenčo, J.; Kuneš, J.; Martinez, A.; Nováková, L.; Cahlíková, L.  [2020]. Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease. Bioorg Chem 2020, 100, 103928.

 

Funding

CURRENT

Target- and ligand-based drug repurposing to control SARS-CoV-2 (CSIC-COVID19-015). CSIC. 15.04.2020 – 14.04.2021. PI: Dr. Carmen Gil

Protein-Guided screening: accelerating drug discovery (PID2019-108587RB-I00). AEI, RETOS Program. 01.06.2020 - 30.05.2023. PI: Dr. Ruth Pérez

Aging and neurodegeneration targeting by protein kinase small molecules inhibitors (PID2019-105600RB-I00). AEI, RETOS Program. 01.06.2020 - 30.05.2023. PI: Dr. Ana Martinez

Multi-target drug design against neurodegenerative diseases (REDES190074). CONICYT, Chile. 01.01.2020 - 31.12.2023. PI: Dr. David Mauricio Ramirez. PI (CSIC): Dr. Ana Martínez

Ensuring long-term sustainability of excellence in chemical biology within Europe and beyond EU-OPENSCREEN-DRIVE (GA 823893). European Union H2020-INFRADEV-2018-2020. 2-2019/2-2023. Coordinator: Prof. Wolfgang Fecke (FMP Berlin). PI (CSIC): Dr. Ana Martínez

Consolidation and strategic positioning of the Spanish node in the ERIC EU-OPENSCREEN network (ES-OPENSCREEN RED2018-102785-E). AEI, Acciones de dinamización “Redes de Investigación. 01.01.2019 - 31.12.2020. PI: Dra. Mabel Loza. PI (CSIC): Dr. Ana Martínez.

Locking cells against Ebola virus (HR18-00469). “La Caixa” Banking Foundation Health Research 2019 Call. 9-2019/9-2022. Coordinator: Dr. Carmen Gil

Design and development of innovative drug for Amyotrophic Lateral Sclerosis (ELA-Madrid-CM) B2017/BMD3813. Programa de actividades de i+D entre grupos de investigación de la Comunidad de Madrid en Biomedicina. 01-2018/12-2022. Coordinator: Dr. Ana Martínez

Myogenic alterations in Amyotrophic Lateral Sclerosis: etiological and therapeutic implications (PIER-0006-2019). Consejería de Salud y Familias 2019. Fundación Pública Andaluza Progreso y Salud. 01.01.2020 - 31.12.2023. PI: Dr. Carmen Paradas. PI (CSIC): Dr. Ana Martínez

Combination of computational, biological and synthetic strategies to be applied in drug development (RTI2018-096100B-100). MINECO, RETOS Program. 1-2019 / 12-2021. IP: Dra. Nuria E. Campillo

DRIVE: Driving next generation autophagy researchers towards translation (MSCA-ITN-ETN GA: 765912). European Union H2020. 11-2017 / 10-2021. Coordinator: Dr Fulvio Regiori. PI (CSIC): Dr. Ana Martínez

Design and Synthesis of broad spectrum antivirals (PIE-201980E024). CSIC, Proyectos Intramurales Especiales. 1-2019/12-2021. PI: Dr. Carmen Gil

Multitarget-designed small molecules targeting protein kinase and BACE1: A new approach for prevention and treatment of cognitive disorders (SAF2016-76693-R). MINECO, RETOS Program. 01.01.2017 - 31.12.2020. PI: Dr. Ana Martinez

PAST

Strengthening the druggability of protein kinases of Leishmania. Drug discovery of specific parasite protein kinase inhibitors (SAF2015-65740-R). MINECO, RETOS Program. 01.01.2016 - 31.07.2019. PIs: Drs. Carmen Gil and Luis Rivas

From fragments to hits: Exploiting the potential of dynamic combinatorial chemistry in drug discovery (CTQ2015-69643-R). MINECO, RETOS Program. 01.01.2016 - 31.12.2018. PI: Dr. Ruth Pérez Fernández

Chemoinformatics to discover multitarget drugs for the treatment of Alzheimer’s disease (CTQ2015-66313-R). MINECO, RETOS Program. 01.01.2016 - 30.09.2018. PI: Drs. Nuria E. Campillo and Angeles Martín Requero

Eyes: a diagnosis window to the brain (SAF2015-72325-EXP). MINECO, EXPLORA Program. 01.06.2016 - 31.05.2017. PI: Dr. Ana Martinez

Development of innovative therapies for Parkinson’s disease (RTC-2015-3439-1). MINECO, RETOS-COLABORACIÓN Program. 01.70-2015 – 31.12-2018. PI: Dr. Ana Martinez

Spanish network of drug discovery (SAF2017-90913-REDT). MINECO Redes de Excelencia Program. 7-2018-6/2020. PI: Mabel Loza (USC). PI (CSIC): Dr. Ana Martínez

Spanish network of drug discovery (SAF2015-71892-REDT). MINECO, Redes de Excelencia Program. 01.01.-2016 – 31.12.2017. PI: Mabel Loza (USC). PI (CSIC): Dr. Ana Martínez

Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target neglected parasitic diseases-PDE4NPD (GA 602666). UE, FP7-Health Program. 1.03.2014 - 28.02.2018. Coordinator: Prof. Rob Leurs (VUA). PI (CSIC): Dr. Carmen Gil

 

More info

Edited Books

libros

Outreach activities

divulga

 

Title: ¿Qué sabemos del Alzheimer?
Ana Martinez
Editorial: CSIC and Catarata ISBN: 978-84-00-08818-7

https://editorial.csic.es/publicaciones/libros/11689/978-84-00-08818-7/el-alzheimer.html

Title: ¿Qué sabemos del Parkinson?
Carmen Gil and Ana Martinez
Editorial: CSIC and Catarata ISBN: 978-0-470-95917-6.
https://editorial.csic.es/publicaciones/libros/12525/0/el-parkinson.html

Title: ¿Qué sabemos de cómo se fabrica un medicamento?
Nuria E. Campillo and María del Carmen Fernández
Editorial: CSIC and Catarata ISBN:
978-84-00-10324-8.
https://editorial.csic.es/publicaciones/libros/13003/0/como-se-fabrica-un-medicamento.html

QSD

Workshops

Madrid Science Week
“Paracetamol synthesis” Hands on workshop for High School students.