Molecular Biophysics and Pharmacology
Finished projects
Development of new, targeting polynuclear platinum and ruthenium complexes for anticancer chemotherapy. Mechanism of action
Programme name: GACR 20-14082J
Coordinator: Institute of Biophysics of the Czech Academy of Sciences
Investigator: Dr. Alexey A. Nazarov, Lomonosov Moscow State University
Years: 2020 - 2022
States participating: Russia
Solver: prof. RNDr. Viktor Brabec, DrSc.
The aim of this project is to obtain data on mechanisms of anticancer action of new, polynuclear platinum and ruthenium complexes; to exploit this knowledge to design new types of metallodrugs acting by fundamentally new mechanisms and exhibit improved anticancer effects than the clinically used metallodrugs.
The next generation of platinum anticancer drugs. Molecular and cellular mechanisms of action
Programme name: INTER-EXCELLENCE
Investigator: James Hoeschele, Eastern Michigan University
Years: 2019 - 2022
States participating: USA
Solver: prof. RNDr. Viktor Brabec, DrSc.
The aim of this project is to improve current knowledge on structure-pharmacological relationships of metallodrugs derived from new platinum complexes and in this way to broaden in a substantial way the theoretical background needed for design and development of new anticancer drugs. The aim of this project will be achieved by obtaining new information on the effects of selected platinum complexes and their combinations with other antitumor agents on structure, conformation and thermodynamic stability of biomolecules (in particular DNA) and on key processes in cells, such as replication, transcription and repair of DNA. This new information will be useful for design and development of a new generation of metallodrugs with truly new mechanism of action and distinct spectrum of biomedical activity.
Epigenetically active substances for tumor chemotherapy
Programme name: INTER-EXCELLENCE
Years: 2017 - 2019
Solver: Viktor Brabec
The major goals of this project are to develop new, epigenetically functioning metallopharmaceuticals, capable of specific targeting of tumor cells including cancer stem cells and to understand the interactions between epigenetically functioning metallopharmaceuticals and biomacromolecules using modern methods of molecular and cellular biophysics and pharmacology
Epigenetic Chemical Biology (EPICHEM)
Programme name: COST Action CM1406
Coordinator: A. Ganesan, University of East Anglia, UK
Years: 2017 - 2019
Solver: Viktor Brabec
Epigenetics refers to dynamic changes that occur at the DNA, RNA and protein level in eukaryotes. Epigenetics is at the heart of gene regulation and determines which genes are activated or silenced. It is of great importance fundamentally and has many exciting translational aspects including therapeutics, microbial pathway engineering and agriculture.
BIOINCMED- Bioinorganic Chemistry for the Design of New Medicines
Programme name: ERC Advanced Grant
Coordinator: P. J. Sadler, University of Warwick, UK
Years: 2013 - 2017
States participating: UK
Solver: Viktor Brabec
Interactions of metallo-drugs on the cellular level
Programme name: COST Action CM1105
Coordinator: P. Bednarski, University of Greifswald, Germany
Years: 2013 - 2017
Solver: Viktor Brabec
It is of utmost importance to understand how metal-based compounds interact with and affect cellular systems, and how they are processed by cells with the goal of developing drugs with novel mechanisms of action. The effects of the potential metallo-drugs on cellular signal-transduction pathways, metal-ion homeostasis, redox responses, cell transformations and cell death are elucidated. Interactions between the designed compounds and selected biomolecules such as metallochaperones, metallotransporters and genetic material are analyzed by both theoretical and experimental methods. The fate of the compounds in cells are studied by measuring metal uptake, speciation and biotransformations, and the elimination of metals and ligands. By better understanding interactions between metal-based compounds and cells, targeted therapeutic strategies with improved specificity can be developed. Hence, within this WG, the processing of metallo-drugs on the cellular level is investigated.
Mechanisms of antitumor effects of non-traditional platinum complexes
Programme name: KONTAKT II
Coordinator: Viktor Brabec, Biofyzikální ústav AV ČR, v. v. i.
Years: 2014 - 2016
States participating: China
Solver: Viktor Brabec
The objective of this project is to improve existing theoretical background on structure-pharmacological activity relationships of metallodrugs and in this way to significantly broaden current knowledge used to design novel anticancer drugs. The aim of this project will be reached by obtaining new information on the effects of selected platinum antitumor drugs on structure, conformation and thermodynamic stability of biomolecules (in particular DNA) and also on the key downstream processes in cells resulting in programmed cell death. These studies will be complementary to those carried out by the partner's laboratory in China. The major motivation for formulation of this aim is to address the urgent clinical need for new therapeutic agents with novel mechanisms of action. The research carried out within this project will contribute to activities of the Czech-Chinese collaboration in research and innovations based on the agreement between the governments of the Czech Republic and China on scientific-technical cooperation.
Molecular and cellular pharmacology of new conjugated organometalic compound. Relations to development of anticancer drugs.
Programme name: COST CZ
Coordinator: Jana Kašpárková, Biofyzikální ústav AV ČR, v. v. i.
Years: 2014 - 2016
Solver: Jana Kašpárková
The main goal of this COST research project will be to increase knowledge and understanding of the design and mechanisms of action of new organometalic conjugates, and to use this enhanced knowledge to develop new classes of organometalic compounds withnovel spectra of biomedical activity. Thus, the aim of this project will be to address the clinical need for new therapeutic agents with novel mechanisms of action. Conjugated organometalic compounds offer such possibilities but their fundamental medicinal chemistry has not been sufficiently explored. Advances in cancer therapy rely on gaining a detailed understanding at the molecular and cellular level of the events which can induce therapeutic agents to destroy cancer cells and yet allow normal cellsto recover. Unique modes of modification of biomolecules by specifically designed organometallic conjugated compounds and the pharmacological factors responsible for antitumor effects including the recognition and processing of biomacromolecule damage will be studied.
Bioinorganic chemistry for the design of new medicines
Programme name: European Commission, FP7, ERC-2009-AdG_20090325
Coordinator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Years: 2010 - 2015
Solver: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Metallo-Drug Design and Action
Programme name: COST – European Cooperation in Science and Technology (EC/NSF)
Coordinator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Investigator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Years: 2006 - 2011
States participating: AT, BE, CHE, DE, DK, ES, FR, GR, HU, IE, IL, IT, NL, NO, PL, PT, RO, SE, SI, TR, UK
Platinum and ruthenium compounds. From DNA damage to cancer chemotherapy
Programme name: Grants for Biomedical Research (Howard Hughes Medical Institute, USA)
Coordinator: Jana Kašpárková, Institute of Biophysics, AS CR, Brno
Years: 2006 - 2010
Platinum and ruthenium complexes. From DNA damage to cancer chemotherapy
Programme name: Collaborative Research Initiative Grant (The Wellcome Trust)
Coordinator: N/A
Investigator: Viktor Brabec, IBP, AS CR, Brno and
Years: 2005 - 2008
States participating: United Kingdom
Mechanistic Studies on New Platinum Clinical Agents
Programme name: National Institutes of Health, NIH, USA
Coordinator: Nicholas P. Farrell, Virginia Commonwealth University, Richmond, USA
Investigator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Years: 1998 - 2007
States participating: USA
Basis for new structure-pharmacological relationship of platinum drugs
Programme name: Grants for Biomedical Research (HHMI, USA)
Coordinator: Jana Kašpárková, Institute of Biophysics, AS CR, Brno
Years: 2001 - 2005
Platinum metal complexes as DNA-protein cross-linking agents
Programme name: National Science Foundation (USA) Academy of Sciences of the Czech Republic
Coordinator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Investigator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
States participating: USA
Transition metal-based anticancer compounds. From mechanistic studies to innovatory cancer chemotherapy
Programme name: Ministry of Education of the CR/Ministry of Education of China
Coordinator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
Investigator: Viktor Brabec, Institute of Biophysics, AS CR, Brno, Czech Republic
States participating: China