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Dr Magdalena Slusarczyk
(she/her)
Research Associate / Trial Manager
Overview
I am a Research Fellow at the School of Pharmacy and Pharmaceutical Sciences, Cardiff University with more than 10 years of research experience in the field of nucleoside phosphate prodrugs. Currently, working as a Research Fellow, I am involved in the anticancer projects aiming to deliver new clinical candidates.
I graduated in Biotechnology in 2001 from Wrocław University of Technology, Poland. Following M.S. degree, I commenced PhD in organic chemistry in K.U. Leuven (Belgium) under the supervision of Prof. Georges Hoornaert. My PhD work was focused on a design, synthesis and biological evaluation of methylene-bridged analogues of biologically active heterocycles.
In 2008, I joined Prof. Chris McGuigan’s group. During the work as a Research Associate, I was involved in many projects including anticancer program that led to discovery of clinical trial agents, such as NUC-1031 (Acelarin) and NUC-3373.
Main scientific interests include chemistry of nucleos(t)ide analogues and phosphate prodrugs, drug discovery and development process in the field of oncology and virology. Recent research interests include clinical research and a design of early phase trials.
Publication
2021
- Slusarczyk, M., Serpi, M., Ghazaly, E., Kariuki, B. M., McGuigan, C. and Pepper, C. 2021. Single diastereomers of the clinical anticancer ProTide agents NUC-1031 and NUC-3373 preferentially target cancer stem cells in vitro. Journal of Medicinal Chemistry 64(12), pp. 8179-8193. (10.1021/acs.jmedchem.0c02194)
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2021. Phosphoramidate nucleoside derivatives as anticancer agents. WO2017207986A1; US20210130387A1 [Patent].
2019
- Bassetto, M. and Slusarczyk, M. 2019. Therapeutic use of fluorinated nucleosides – progress in patents. Pharmaceutical Patent Analyst 7(6), pp. 277. (10.4155/ppa-2018-0028)
2018
- Slusarczyk, M., Ferrari, V., Serpi, M., Gonczy, B., Balzarini, J. and McGuigan, C. 2018. Symmetrical diamidates as a class of phosphate prodrugs to deliver the 5'-monophosphate form of anticancer nucleoside analogues. ChemMedChem 13(21), pp. 2305-2316. (10.1002/cmdc.201800504)
- Slusarczyk, M., Serpi, M. and Pertusati, F. 2018. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antiviral Chemistry and Chemotherapy 26, pp. 1-31. (10.1177/2040206618775243)
- Slusarczyk, M., Ferla, S., Brancale, A. and McGuigan, C. 2018. Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides. Bioorganic and Medicinal Chemistry 26(3), pp. 551-565. (10.1016/j.bmc.2017.11.037)
2017
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2017. Adenosine derivatives for use in the treatment of cancer. WO2017207989A1 [Patent].
- Cavaliere, A., Probst, K., Westwell, A. and Slusarczyk, M. 2017. Fluorinated nucleosides as an important class of anticancer and antiviral agents. Future Medicinal Chemistry 9(15)
- Serpi, M., De Biasi, R., Pertusati, F., Slusarczyk, M. and McGuigan, C. 2017. Synthetic approaches for the preparation of phosphoramidate prodrugs of 2’-deoxypseudoisocytidine. ChemistryOpen 6(3), pp. 424-436. (10.1002/open.201700019)
2016
- McGuigan, C. et al. 2016. Anti-flavivirus activity of different tritylated pyrimidine and purine nucleoside analogues. ChemistryOpen 5(3), pp. 227-235. (10.1002/open.201500216)
2015
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2015. Gemcitabine Prodrugs. WO 2015/198058; GB51857 [Patent].
2014
- Slusarczyk, M. et al. 2014. Application of ProTide technology to Gemcitabine: A successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. Journal of Medicinal Chemistry 57(4), pp. 1531-1542. (10.1021/jm401853a)
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2014. Prodrug. IN 2014MU02050 [Patent].
2013
- McGuigan, C. et al. 2013. Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides. European Journal of Medicinal Chemistry 70, pp. 326-340. (10.1016/j.ejmech.2013.09.047)
- Ghazaly, E. A. et al. 2013. ProGem1: Phase I first-in-human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors [Abstract]. Journal of Clinical Oncology 31(15), article number: abstr. 2576.
2012
- McGuigan, C., Balzarini, J., Slusarczyk, M., Gonczy, B. and Murziani, P. 2012. Phosphoramidate derivatives of 5 - fluoro - 2 ' - deoxyuridine for use in the treatment of cancer. WO 2012117246 A1 20120907 [Patent].
2011
- McGuigan, C., Murziani, P., Slusarczyk, M., Gonczy, B., Vande Voorde, J., Liekens, S. and Balzarini, J. 2011. Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the preformed bioactive monophosphate in cells and confer advantage over the parent nucleoside. Journal of Medicinal Chemistry 54(20), pp. 7247-7258. (10.1021/jm200815w)
- Voorde, J. V., Liekens, S., McGuigan, C., Murziani, P. G. S., Slusarczyk, M. and Balzarini, J. 2011. The cytostatic activity of NUC-3073, a phosphoramidate prodrug of 5-fluoro-2 '-deoxyuridine, is independent of activation by thymidine kinase and insensitive to degradation by phosphorolytic enzymes. Biochemical Pharmacology 82(5), pp. 441-452. (10.1016/j.bcp.2011.05.024)
2008
- Slusarczyk, M., De Borggraeve, W. M., Hoornaert, G., Deroose, F. and Linders, J. T. M. 2008. Synthesis and biological evaluation of methylene-bridged analogs of the potent cannabinoid receptor antagonist rimonabant. European Journal of Organic Chemistry 2008(8), pp. 1350-1357. (10.1002/ejoc.200700960)
Articles
- Slusarczyk, M., Serpi, M., Ghazaly, E., Kariuki, B. M., McGuigan, C. and Pepper, C. 2021. Single diastereomers of the clinical anticancer ProTide agents NUC-1031 and NUC-3373 preferentially target cancer stem cells in vitro. Journal of Medicinal Chemistry 64(12), pp. 8179-8193. (10.1021/acs.jmedchem.0c02194)
- Bassetto, M. and Slusarczyk, M. 2019. Therapeutic use of fluorinated nucleosides – progress in patents. Pharmaceutical Patent Analyst 7(6), pp. 277. (10.4155/ppa-2018-0028)
- Slusarczyk, M., Ferrari, V., Serpi, M., Gonczy, B., Balzarini, J. and McGuigan, C. 2018. Symmetrical diamidates as a class of phosphate prodrugs to deliver the 5'-monophosphate form of anticancer nucleoside analogues. ChemMedChem 13(21), pp. 2305-2316. (10.1002/cmdc.201800504)
- Slusarczyk, M., Serpi, M. and Pertusati, F. 2018. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antiviral Chemistry and Chemotherapy 26, pp. 1-31. (10.1177/2040206618775243)
- Slusarczyk, M., Ferla, S., Brancale, A. and McGuigan, C. 2018. Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides. Bioorganic and Medicinal Chemistry 26(3), pp. 551-565. (10.1016/j.bmc.2017.11.037)
- Cavaliere, A., Probst, K., Westwell, A. and Slusarczyk, M. 2017. Fluorinated nucleosides as an important class of anticancer and antiviral agents. Future Medicinal Chemistry 9(15)
- Serpi, M., De Biasi, R., Pertusati, F., Slusarczyk, M. and McGuigan, C. 2017. Synthetic approaches for the preparation of phosphoramidate prodrugs of 2’-deoxypseudoisocytidine. ChemistryOpen 6(3), pp. 424-436. (10.1002/open.201700019)
- McGuigan, C. et al. 2016. Anti-flavivirus activity of different tritylated pyrimidine and purine nucleoside analogues. ChemistryOpen 5(3), pp. 227-235. (10.1002/open.201500216)
- Slusarczyk, M. et al. 2014. Application of ProTide technology to Gemcitabine: A successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. Journal of Medicinal Chemistry 57(4), pp. 1531-1542. (10.1021/jm401853a)
- McGuigan, C. et al. 2013. Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides. European Journal of Medicinal Chemistry 70, pp. 326-340. (10.1016/j.ejmech.2013.09.047)
- Ghazaly, E. A. et al. 2013. ProGem1: Phase I first-in-human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors [Abstract]. Journal of Clinical Oncology 31(15), article number: abstr. 2576.
- McGuigan, C., Murziani, P., Slusarczyk, M., Gonczy, B., Vande Voorde, J., Liekens, S. and Balzarini, J. 2011. Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the preformed bioactive monophosphate in cells and confer advantage over the parent nucleoside. Journal of Medicinal Chemistry 54(20), pp. 7247-7258. (10.1021/jm200815w)
- Voorde, J. V., Liekens, S., McGuigan, C., Murziani, P. G. S., Slusarczyk, M. and Balzarini, J. 2011. The cytostatic activity of NUC-3073, a phosphoramidate prodrug of 5-fluoro-2 '-deoxyuridine, is independent of activation by thymidine kinase and insensitive to degradation by phosphorolytic enzymes. Biochemical Pharmacology 82(5), pp. 441-452. (10.1016/j.bcp.2011.05.024)
- Slusarczyk, M., De Borggraeve, W. M., Hoornaert, G., Deroose, F. and Linders, J. T. M. 2008. Synthesis and biological evaluation of methylene-bridged analogs of the potent cannabinoid receptor antagonist rimonabant. European Journal of Organic Chemistry 2008(8), pp. 1350-1357. (10.1002/ejoc.200700960)
Patents
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2021. Phosphoramidate nucleoside derivatives as anticancer agents. WO2017207986A1; US20210130387A1 [Patent].
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2017. Adenosine derivatives for use in the treatment of cancer. WO2017207989A1 [Patent].
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2015. Gemcitabine Prodrugs. WO 2015/198058; GB51857 [Patent].
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2014. Prodrug. IN 2014MU02050 [Patent].
- McGuigan, C., Balzarini, J., Slusarczyk, M., Gonczy, B. and Murziani, P. 2012. Phosphoramidate derivatives of 5 - fluoro - 2 ' - deoxyuridine for use in the treatment of cancer. WO 2012117246 A1 20120907 [Patent].
Research
To date my research has been largely focused on the rational design and synthesis of nucleoside phosphate prodrugs with potential anticancer activity using the ProTide technology. This approach, applied to the both anticancer and antiviral clinical or non-clinical nucleoside analogue (NA) therapeutics can significantly enhance their therapeutic efficacy by overcoming the key resistance mechanisms associated with the clinical use of NAs such as uptake, activation and breakdown. My research is externally funded by NuCana plc, a clinical-stage biopharmaceutical company based in Edinburgh, with our main interest in developing anticancer medicines to significantly improve treatment outcomes for patients. The over-decade collaboration with NuCana led to the discovery and clinical development of the three ProTide agents, Acelarin, NUC-3373 and NUC-7738. The most clinically advanced Acelarin (NUC-1031), the ProTide transformation of gemcitabine, in June 2019 received orphan drug designation from the FDA for the treatment of biliary tract cancer. Current collaboration with the scientists at the University of Sussex, Brighton and Sussex Medical School and University of St Andrews, School of Medicine is focused on screening and understanding the potential mechanisms of action of novel ProTides in different cancer cell lines.
In the past, in collaboration with Rega Institute, I was involved in many projects aiming to design, synthesise and biologically evaluate compounds against different types of viruses.
Biography
Qualifications
- M.S degree in Biotechnology, Wrocław University of Technology, Poland, 2001
- PhD in Organic Chemistry, K.U. Leuven, Belgium, 2007
- MSc in Clinical Research, Cardiff University, 2023
Key expertise areas
- Heterocyclic and medicinal chemistry
- Nucleos(t)ide analogues and phosphate prodrugs chemistry
- Diastereomers separation, HPLC chromatography
- NMR spectroscopy
- Mass spectrometry
- UV-Vis spectroscopy
- Enzymatic assays
- Drug discovery and development process in the field of oncology
- Clinical Trial Management (IMP and non-IMP)