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个人简介
Degree in Pharmacy and PhD (Universidad de Salamanca). Predoctoral (Louisiana State University LSU 1991) and Postdoctoral (University of California, Los Angeles UCLA 1991-1993; Universidad de Alcalá UAH 1994-1996 and BASF AG, Ludwigshafen 1999) experience.
Full Professor of Organic Chemistry (2009) at Universidad San Pablo CEU (USPCEU) and Dean of Faculty of Pharmacy (2008-2022). President of the Board of Deans of Faculties of Pharmacy of Spain (2018-2022). Since July 2018, President of the Spanish Society of Medicinal Chemistry (SEQT) and since 2013 Coordinator of the PhD Program on Science and Technology of Health that belongs to CEINDO (CEU International School of Doctoral Studies).
Council member of the European Federation of Medicinal Chemistry and Chemical Biology (EFMC) since 2018 and elected Treasurer of the Executive Committee of the EFMC starting January 2023.
In the period 1988-1991 she worked in the field of natural products chemistry (Tetrahedron 1988, 1995 y 1996, Phytochemistry 1992, 1992, 1992 y 1993) and later she specialized in the use of computational techniques for the study of stereospecificity of the Diels-Alder reactions in the group of Prof. K. N. Houk in UCLA (JACS, 1995, TL 1994, 1996). In this period, she participated in one of the first works on the design of a catalytic antibody able to control the evolution of this reaction (Science 1993). In the next years, she continued specialization in the computer-aided study of drug receptor interactions, molecular recognition processes and drug design in the group of Prof. F. Gago at UAH (JMC. 1996, 2002, 2004; J. of Computer-Aided Mol. Des. 1997; JOC. 1996, 1997, 1999).
Since 1996, after incorporation to USPCEU, I work in medicinal chemistry, mainly in the development of new antitumor agents. I supervise, in collaboration with Dr. Ana Ramos, a multidisciplinary research group with experts in molecular modelling techniques and organic synthesis. We carry out also biological assays in isolated targets and cells, and we count with stablished collaborations for more specific in vitro and in vivo experiments. In this period, we have described many antitumor agents with activity as DNA intercalators, enzyme inhibitors (CDKs, MMPs, HDAC, CK2, Calpains), receptor and peptide modulators (ER, adrenomedullin, PAMP). Our main achievement is the development of potent and specific inhibitors of MMP2 (Matrix metalloprotease type 2), with high selectivity against MMP9, the other gelatinase. Recently we have used the same methodology to design blood-brain barrier permeable molecules to inhibit Protein Tyrosine-Phosphatase Receptor Z1 (PTPRZ1), mimicking the activity of its endogenous ligand, Pleiotrophin. In vitro and in vivo tests confirm our hypothesis that PTPRZ1 is a novel target for the treatment of alcoholism and Parkinson’s disease.
We also worked in the hypothermia induction by small molecule mimicry, with the aim of offering an innovative, cheap, and efficacious treatment to prevent or delay combat-related
ocular injuries.
Recently we started working on the design of multitargeted agents, a strategy that has shown many advantages compared to combined therapies in complex diseases such as cancer. Protein kinase 2 (CK2) and histone deacetylase (HDAC) are two enzymes involved in cancer. CK2 plays an important role in HDAC regulation; therefore, our hypothesis was that the design of dual inhibitors of these two enzymes was an interesting strategy to develop drugs against this disease. We have obtained several series of dual inhibitors using known CK2 ligands (TBB, DMAP, CX4945), connected to various Zinc Binding Groups (ZBGs), such as hydroxamates, carboxylic acids and benzamides. All this research has been funded by national and international grants with over 950.000€
We are now working on: a) the synthesis of a series of PET and fluorescent radioligands for the detection of MMP2 and MMP13. b) the development of PROTACs (Proteolysis Targeting Chimeras) for the degradation of HDAC and CK2 making use of CRBN and VHL E3 ligases. c) the design of LYTACs (LYsosome TArgeting Chimaeras) for the degradation of extracellular enzymes MMP2/MMP13 starting from the highly active inhibitors described by our group. d) the development of folate conjugates as a drug delivery strategy for our beyond the Rule of five (bRo5) compounds.
Supervision of 9 PhD thesis (4 of them with international label) and a large number of Master and Bachelor Degree Projects.
研究兴趣
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NEUROPHARMACOLOGY (2023)
Frontiers in pharmacology (2023): 1252184-1252184
Neuropharmacology (2023): 109438-109438
M. Galan-Llario, M. Rodriguez-Zapata, T. Fontan,E. Gramage,M. Vicente-Rodriguez,C. Perez-Garcia,J. M. Zapico,J. Sevillano, M. P. Ramos-Alvarez,A. Ramos,B. de Pascual-Teresa,G. Herradon
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