Ramírez Lab

Pharmacoinformatics & Drug Design

Welcome to the Ramírez Lab

We are a multidisciplinary group focused on the study of biomolecular systems by using theoretical and experimental approaches. We aim to use computational polypharmacology with wet lab analyses to strengthen the drug design and development processes. Our work involves collaboration with medicinal chemists, biochemists, and biologists, and we are part of the Pharmacology Department - Faculty of Biological Sciences at University of Concepción.

Active research areas

  • Structural insights into the substrate specificity and transport mechanisms in the Nitrate/Peptide Transporter (NPF) Family

  • Computational polypharmacology: Multi-target drug design against neurodegenerative diseases

  • Drug design of novel antimicrobial agents

  • Understanding the binding mechanisms of endo and phytocannabinoids into the human CB1 receptor

  • Latest publication

    From kinase inhibitors to multitarget ligands as powerful drug leads for Alzheimer’s disease using protein-templated synthesis

    Nozal, V., García-Rubia, A., Cuevas, E., Pérez, C., Tosat-Bitrián, C., Bartolomé, F., Carro, E., Ramírez, D., Palomo, V., and Martínez, A.

    Angewandte Chemie International Edition, 2021, DOI: 10.1002/anie.202106295

    Multitarget directed ligands (MTDLs) are arising as promising tools to tackle complex diseases. The main goal of this work is to create powerful modulating agents for neurodegenerative disorders. To achieve this aim, we have combined fragments that inhibit key protein kinases involved in the main pathomolecular pathways of Alzheimer’s disease (AD) such as tau aggregation, neuroinflammation and decreased neurogenesis, whilst looking for a third action in beta-secretase (BACE1), responsible of β-amyloid production. We obtained well-balanced MTDLs with in vitro activity in three different relevant targets and efficacy in two cellular models of AD. Furthermore, computational studies confirmed how these compounds accommodate adequately into the long and rather narrow BACE1 catalytic site. Finally, we employed in situ click chemistry using BACE1 as protein template as a versatile synthetic tool that allowed us to obtain further MTDLs.

    Funding

    Grant Funded by Role Date
    Reposicionamiento de medicamentos para tratamiento de la pandemia por coronavirus (COVID-19). Chile - ANID No. COVID0199 Principal Investigator 2020 - 2021
    Actualización de los servicios de ANSEP (Astrocyte-neuron simulation environment platform) bajo el estudio integrativo de enfermedades neurodegenerativas. Colombia - Pontificia Universidad Javeriana Associate Investigator 2021 - 2022
    Target- and ligand-based drugs to control SARS-CoV-2 pandemic (CoV2Drugs). Spain - CSIC-COV19-015 Associate Investigator 2020 - 2021
    Multi-Target Drug Design Against Neurodegenerative Diseases. Chile - Conicyt No. REDES190074 Principal Investigator 2020 - 2021
    INSECTR – International Network to Study Secondary Metabolite Transport In Plants. Chile - Conicyt No. REDES1900254 Associate Investigator 2020 - 2021
    Identificación de reacciones controladoras de lipotoxicidad inducida por ácido palmítico en un modelo computacional multiómico astrocitario. Colombia - Colciencias No. 67270 Associate Investigator 2020 - 2022
    Scholarship Programme for Young Professors and Researchers from Latin American Universities. Spain - Coimbra group Principal Investigator 2019
    Structural insights into the substrate specificity and transport mechanisms in the Nitrate/Peptide Transporter (NPF) Family. Chile - Fondecyt No. 11180604 Principal Investigator 2018 – 2021
    Análisis metabolómico de los efectos neuroprotectores de la tibolona en un modelo astrocitico humano de lipotoxicidad con ácido palmítico. Colombia - Colciencias International Advisor 2017 - 2020