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Design, synthesis, and study of new biologically active compounds and their preclinical and clinical development as potential anticancer pharmaceuticals. Development of biologically accessible formulations, drug systems, and therapeutic methods aimed at the treatment of cancer and leukaemias. These are the core goals of Research Programme 2 as presented by the programme\u2019s leaders Michal Hocek and Mari\u00e1n Hajd\u00fach.<\/b><\/p>\n
Research Programme 2 (RP2) focuses on the development of new bioactive compounds as potential therapeuticals and on the development of new therapeutic methods for the treatment of tumours and leukaemias. The initial stage of this process focuses on the design and synthesis of new substances and on libraries of substances or (bio)macromolecules, which are then tested in enzyme or cell assays. Selected active substances are subsequently optimised for better solubility, pharmacokinetics, low toxicity, and higher effectivity. The most promising substances are tested in <\/span>in vivo <\/span><\/i>models aimed at identifying candidates for clinical testing. The programme also aims at preparation of biologically available formulations, prodrugs, polymer carriers, and other drug systems. Last but not least, RP2 is active in the development of new, more effective, and better tolerated therapeutical methods.<\/span><\/p>\n RP2 brings together 29 teams from 10 leading institutions, which work on various aspects of development of potential anticancer drugs and therapeutic methods. Their efforts focus on the development of new therapeutic substances on the basis of small molecules, polymers, and so-called biologicals (therapeutic proteins, nucleic acids, and cell therapies) and include also optimisation of candidate substances, biological testing, and preclinical development.\u00a0<\/span><\/p>\n Michal Hocek\u2019s group from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences develops in collaboration with Marian Hajd\u00fach\u2019s team from the Institute of Molecular and Translational Medicine of the Faculty of Medicine of Palacky University anticancer pharmaceuticals on the basis of modified nucleosides, which cause DNA damage and apoptosis. They also develop and study specific inhibitors of key protein kinases and ligands or inhibitors of cell receptors.\u00a0<\/span><\/p>\n Zuzana Ke\u010dk\u00e9\u0161ov\u00e1 and her team from the Institute of Organic Chemistry and Biochemistry studies antitumour proteins and develops small molecules capable of activating and stabilising these proteins.\u00a0<\/span><\/p>\n The teams of Vladim\u00edr Kry\u0161tof and Vladim\u00edr Divok\u00fd from the Institute of Molecular and Translational Medicine have in collaboration developed a unique inhibitor of oncogenic tyrosine kinases that has a potential in the treatment of acute leukaemia with a mixed phenotype.\u00a0<\/span><\/p>\n Ji\u0159\u00ed Neu\u017eil\u2019s team from the Institute of Biotechnology of the Czech Academy of Sciences is currently successfully conducting clinical testing of the MitoTam substance aimed at a treatment of kidney cancer. At the same institute, Cyril Ba\u0159inka\u2019s team is researching bispecific \u2018lures\u2019 that mediate interaction between immune cells and cancer cells in order to achieve selective destruction of the latter.\u00a0<\/span><\/p>\n The team of Tereza Ormsby and Jan Konvalinka from the Institute of Organic Chemistry and Biochemistry is, in collaboration with Tom\u00e1\u0161 Etrych\u2019s team from the Institute of Macromolecular Chemistry of the Czech Academy of Sciences, developing and testing synthetic analogues of antibodies, so-called iBodies, which are used in therapeutic applications to activate the immune system and achieve targeted destruction of cancer cells.<\/span><\/p>\n Scientists led by Tom\u00e1\u0161 Etrych from Institute of Macromolecular Chemistry and Marek Kov\u00e1\u0159 from the Institute of Microbiology of the Czech Academy of Sciences develop macromolecular conjugates carrying cytostatics for targeted antitumour treatment and polymer probes to aid visualisation of tumours in directed surgery.\u00a0<\/span><\/p>\n In conclusion, it is fair to say that the research teams of RP2 have achieved significant progress in the development of new compounds with potential for preclinical and clinical testing as candidates for original antitumour pharmaceuticals. The teams closely collaborate in both the development and the testing with other research programmes of the NICR, especially with RP1, which focuses on the study of molecular mechanisms of cancers and identification of prognostic, stratification, and therapeutic targets, eventually their validation in cell or animal models. Our target for the next few years is to take several of the most promising substances to the stage of clinical testing.\u00a0<\/span><\/p>\n References:<\/span><\/i><\/p>\n M. R. Zamani, M. Hadzima, K. Bla\u017ekov\u00e1, V. \u0160ubr, T. Ormsby, J. Celis-Gutierrez, B. Malissen, L. Kostka, T. Etrych, P. \u0160\u00e1cha, J. Konvalinka, Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker. J. Biol. Chem. 300, 107325 (2024). DOI: <\/i>10.1016\/j.jbc.2024.107325<\/i><\/a><\/p>\n R. Pola, E. Grosmanov\u00e1, M. Pechar, D. Hor\u00e1k, T. Krunclov\u00e1, J. Pankr\u00e1c, M. Henry, M. Ka\u0148a, J. Bou\u010dek, L. \u0160efc, J.-L. Coll, T. Etrych, Stimuli-Responsive Polymer Nanoprobes Intended for Fluorescence-Guided Surgery of Malignant Head-and-Neck Tumors and Metastases. Adv. Healthc. Mater. 12, e2301183 (2023). DOI: <\/span><\/i>10.1002\/adhm.202301183\u00a0<\/span><\/i><\/a><\/p>\n","protected":false},"excerpt":{"rendered":" Design, synthesis, and study of new biologically active compounds and their preclinical and clinical development as potential anticancer pharmaceuticals. Development of biologically accessible formulations, drug systems, and therapeutic methods aimed at the treatment of cancer and leukaemias. These are the core goals of Research Programme 2 as presented by the programme\u2019s leaders Michal Hocek and Mari\u00e1n Hajd\u00fach.<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[98,78,84],"tags":[],"class_list":["post-3640","post","type-post","status-publish","format-standard","hentry","category-2024-4","category-newsletter-inscider-en","category-sciprogramme-newsletter-inscider-en"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3640","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/comments?post=3640"}],"version-history":[{"count":2,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3640\/revisions"}],"predecessor-version":[{"id":3687,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3640\/revisions\/3687"}],"wp:attachment":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/media?parent=3640"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/categories?post=3640"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/tags?post=3640"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}From the most interesting results of RP2<\/b><\/h4>\n
New molecules for preclinical and clinical testing\u00a0<\/b><\/h4>\n