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Dr Magdalena Slusarczyk
(hi/ei)
Rheolwr Cyswllt Ymchwil / Treial
Trosolwyg
Rwy'n Gymrawd Ymchwil yn yr Ysgol Fferylliaeth a'r Gwyddorau Fferyllol, Prifysgol Caerdydd gyda mwy na 10 mlynedd o brofiad ymchwil ym maes prodrugs ffosffad niwcleoside. Ar hyn o bryd, gan weithio fel Cymrawd Ymchwil, rwy'n ymwneud â'r prosiectau gwrth-ganser sy'n anelu at gyflwyno ymgeiswyr clinigol newydd.
Graddiais mewn Biotechnoleg yn 2001 o Brifysgol Technoleg Wrocław, Gwlad Pwyl. Yn dilyn gradd M.S. dechreuais PhD mewn cemeg organig yn K.U. Leuven (Gwlad Belg) dan oruchwyliaeth yr Athro Georges Hoornaert. Roedd fy ngwaith PhD yn canolbwyntio ar ddylunio, synthesis a gwerthusiad biolegol o analogau methylene-pontydd heterocycles biolegol.
Yn 2008, ymunais â grŵp yr Athro Chris McGuigan. Yn ystod y gwaith fel Cydymaith Ymchwil, roeddwn yn ymwneud â llawer o brosiectau gan gynnwys rhaglen gwrthganser a arweiniodd at ddarganfod asiantau treialon clinigol, megis NUC-1031 (Acelarin) a NUC-3373.
Mae'r prif ddiddordebau gwyddonol yn cynnwys cemeg niwclews (t) analogau ide a prodrugs, proses darganfod cyffuriau a datblygu ym maes oncoleg a firoleg. Mae diddordebau ymchwil diweddar yn cynnwys ymchwil glinigol a dyluniad treialon cam cynnar.
Cyhoeddiad
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].
Ymchwil
Hyd yma mae fy ymchwil wedi canolbwyntio'n bennaf ar ddylunio a synthesis rhesymegol prodrugs ffosffad niwcleosid gyda gweithgaredd gwrth-ganser posibl gan ddefnyddio'r dechnoleg ProTide. Gall y dull hwn, a gymhwysir i'r therapiwteg niwcleosid anticancer a gwrthfeirysol clinigol neu anghlinigol analog (NA) wella eu heffeithiolrwydd therapiwtig yn sylweddol trwy oresgyn y mecanweithiau gwrthiant allweddol sy'n gysylltiedig â defnyddio NAs yn glinigol fel derbyn, actifadu a chwalu. Mae fy ymchwil yn cael ei ariannu'n allanol gan NuCana plc, cwmni biofferyllol cyfnod clinigol yng Nghaeredin, gyda'n prif ddiddordeb mewn datblygu meddyginiaethau gwrth-ganser i wella canlyniadau triniaeth i gleifion yn sylweddol. Arweiniodd y cydweithrediad dros ddegawd â NuCana at ddarganfod a datblygu clinigol y tri asiant ProTide, Acelarin, NUC-3373 a NUC-7738. Derbyniodd y Acelarin mwyaf datblygedig yn glinigol (NUC-1031), trawsnewidiad ProTide gemcitabine, ym mis Mehefin 2019 ddynodiad cyffuriau amddifad gan yr FDA ar gyfer trin canser y llwybr deuol. Ar y cyd â gwyddonwyr Ysgol Feddygol Prifysgol Sussex, Brighton and Sussex a Phrifysgol St Andrews, mae'r Ysgol Meddygaeth yn canolbwyntio ar sgrinio a deall mecanweithiau gweithredu posibl ProTides newydd mewn gwahanol linellau celloedd canser.
Yn y gorffennol, mewn cydweithrediad â Sefydliad Rega, roeddwn yn ymwneud â llawer o brosiectau gyda'r nod o ddylunio, synthesis a gwerthuso cyfansoddion yn fiolegol yn erbyn gwahanol fathau o firysau.
Bywgraffiad
Cymwysterau
- Gradd M.S mewn Biotechnoleg, Prifysgol Technoleg Wrocław, Gwlad Pwyl, 2001
- PhD mewn Cemeg Organig, KU Leuven, Gwlad Belg, 2007
- MSc mewn Ymchwil Glinigol, Prifysgol Caerdydd, 2023
Meysydd arbenigedd allweddol
- Cemeg heterocyclaidd a meddyginiaethol
- Nucleos (t) analogau ide a chemeg prodrugs ffosffad
- Gwahaniad diastereomers, cromatograffeg HPLC
- Sbectrosgopeg NMR
- Sbectrometreg màs
- Sbectrosgopeg UV-VIS
- Profion ensymatig
- Proses darganfod a datblygu cyffuriau ym maes oncoleg
- Rheoli Treial Clinigol (IMP a heb IMP)