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Assistant Professor Esther WOON

BSc (Pharm) (Hons), National University of Singapore
PhD (Medicinal Chemistry), University of Bath, UK
University of Oxford, UK (Post Doc)
UCL School of Pharmacy, UK (Post Doc)

Department of Pharmacy, National University of Singapore
18 Science Drive 4, Singapore 117543
Tel: +65 6516 2932
Fax: +65 6779 1554
Email: esther.woon@nus.edu.sg

Teaching Activities in NUS

I am currently involved in teaching the following modules:

  • PR2115 Medicinal Chemistry for Drug Design (Module Coordinator)
  • PR4105 Natural Products
  • PR4205 Bioorganic Principles of Medicinal Chemistry (Lectures on Epigenetics)

Our group is fascinated by how environmental factors such as diet, lifestyle, behaviour and emotional state can alter the way in which our genes are expressed. This is achieved primarily through chemical modifications on DNA, RNA and histone proteins, without any change in the underlying DNA sequence. The study of how these modifications interact with each other to bring about gene regulation is known as epigenetics. Importantly, dysregulation of these epigenetic processes provide the mechanism to many of the human diseases, such as cancer, metabolic disorders and neurodegenerative diseases. They also appear to be heritable, allowing one generation to pass on gene expression patterns (along with disease susceptibility or protection) to the next generation.

Our research seeks to understand the epigenetic basis of diseases through the discovery of small molecule probe and inhibitors. We use a combination of approaches in our studies, including organic synthesis, molecular modelling, structure-based design, molecular biology, biochemical assays and biophysical techniques, such as X-ray crystallography, mass spectrometry (non-denaturing ESI-MS, MALDI-TOF), DSF, ITC, SPR and CD analyses.

25. Zou, S.; Toh, J. D. W.; Wong, K. H. Q.; Gao, Y-G., Hong, W.; Woon, E. C. Y.* N6-Methyladenosine: a conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5. Scientific Reports, 2016, 6:25677; doi:10.1038/srep25677.

IF: 5.578  [PDF] [LINK]

24. Yang, T.; Cheong, A.; Mai, X.; Zou, S.; Woon. E. C. Y.* A methylation-switchable conformational probe for sensitive and selective detection of RNA demethylase activity. Chemical Communications, 2016, 52, 6181-6184.

IF: 6.834  [PDF] [LINK]

23. Lim, A.; Zhou, J.; Sinha, R. A.; Singh, B. K.; Ghosh, S.; Lim, K. H.; Chow, P. K. H.; Woon, E. C. Y. and Yen, P. M. Hepatic FTO expression is increased in NASH and its silencing attenuates palmitate acid-induced lipotoxicity. Biochemical and Biophysical Research Communications, 2016, 479, 476-481.

IF: 2.297  [PDF] [LINK]

22. Paine, H. A.; Nathubhai, A.; Woon, E. C. Y.; Sunderland, P. T.; Wood, P. J.; Mahon, M. F.; Lloyd, M. D.; Thompson, A. S.; Haikarainen, T.; Narwal, M. et al. Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors in vitro. Bioorganic & Medicinal Chemistry, 2015, 23, 5891-5908.

IF: 3.151  [PDF] [LINK]

21. Toh, J. D. W.; Sun, L.; Lau, L. Z. M.; Tan, J.; Low, J. J. A.; Tang, C. W. Q.; Cheong, E. J. Y.; Tan, M. J. H.; Chen, Y.; Hong, W.; Gao, Y-G*., Woon. E. C. Y.* A Strategy Based on Nucleotide Specificity Leads to Selective Inhibition of N6-Methyladenosine Demethylase FTO. Chemical Science, 2015, 6, 112-122.

**Work featured in Front Cover Image in inaugural online edition 

IF: 9.211  [PDF] [LINK]

20. Woon, E. C. Y.;Sunderland, P. T.; Paine, H. A.; et. al. One-pot tandem Hurtley–retro-Claisen–cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs. Bioorganic & Medicinal Chemistry, 2013, 21, 5218-5227.

IF: 3.151  [PDF] [LINK]

19. Singh, N.: challiday, A.; Thomas, J.; Kuznetsova, O.; Baldwin, R.; Woon, E. C. Y.; Aley, P.; Antoniadou, I.; Sharp, T.; Vasudevan, S.; Churchill, G.A safe lithium mimetic for bipolar disorder. Nature Communications, 2013, 4, article no. 1332, doi:10.1038/ncomms2320.      

IF: 11.470  [PDF] [LINK]

18. Demetriades, M.; Leung, I. K. H.; Ratcliffe, P. J.; Woon, E. C. Y.;* Schofield, C. J.* Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors. Angewandte Chemie International Edition, 2012, 51, 6672-6675.

*co-corresponding author

invention featured in SciBX      

IF: 13.455  [PDF] [LINK]

17. Woon, E. C. Y; Tumber, A.; Kawamura, A.; et. al. Linking of 2-oxoglutarate and substrate binding sites enables potent and highly selective inhibition of JmjC histone demethylases. Angewandte Chemie International Edition, 2012, 51, 1631-1634.

**highlighted as ‘Hot Paper’. 

IF: 13.455  [PDF] [LINK]

16. Woon, E. C. Y; Demetriades, M.; Bagg, E. A. L. et. al. Dynamic combinatorial mass spectrometry leads to inhibitors of a 2‑oxoglutarate dependent nucleic acid demethylase. Journal of Medicinal Chemistry, 2012, 55, 2173-2184.

IF: 5.447  [PDF] [LINK]

15. Rose, N. R.*, Woon, E. C. Y.*; Walport, L.; et. al. The Plant Growth Regulator Daminozide is a Selective Inhibitor of the KDM2/7 Histone Demethylases. Journal of Medicinal Chemistry, 2012, 55, 6639-6643.

*co-first authorship

IF: 5.447  [PDF] [LINK]

14. Yeoh, K. K.; Chan, M. C.; Thalhammer, A.; Demetriades, M.; Chowdhury, R.; Tian, Y. M.; Stolze, I.; McNeill, L. A.; Lee, M. G.; Woon, E. C. Y.; Mackeen, M.;et. al. Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron. Organic & Biomolecular Chemistry, 2013, 11, 732-745 DOI: 1039/C2OB26648B.

IF: 3.696  [PDF] [LINK]

13. Contreras-Martel, C.*; Amoroso, A.*; Woon, E. C. Y.*; Zervosen, A.*; et. al. Structure-guided design of cell wall biosynthesis inhibitors that overcome β‑lactam resistance in Staphylococcus aureus (MRSA). ACS Chemical Biology, 2011, 6, 943‑951.

*co-first authorship     

IF: 6.446  [PDF] [LINK]

12. Woon, E. C. Y; Zervosen, A.; Sauvage, E.; et. al. Structure guided development of potent reversibly binding penicillin binding protein inhibitors. ACS Medicinal Chemistry Letter, 2011, 2, 219-223.

IF: 3.355  [PDF] [LINK]

11. Chowdhury, R.; Yeoh, K. K.; Tian, Y. M.; Hillringhaus, L.; Bagg, E. A.; Rose, N. R.; Leung, I. K. H.; Li, X. S.; Woon, E. C. Y.; Yang, M.; et. al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO reports, 2011, 12, 463-469.

IF: 9.055  [PDF] [LINK]

10. Sunderland, P. T.; Woon, E. C. Y.; Dhami, A.; et. al. 5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2). Journal of Medicinal Chemistry, 2011, 54, 2049-2059.

IF: 5.447  [PDF] [LINK]

9. Chang, K. H.; King, O. N. F.; Tumber, A.; Woon, E. C. Y.; Heightman, T. D.; McDonough, M. A.; Schofield, C. J.; Rose, N. R. Inhibition of histone demethylases by 4‑carboxy‑2,2’‑bipyridyl compounds. ChemMedChem, 2011, 6, 759-764.

**Highlighted as ‘Very Important Paper’ 

IF: 3.306  [PDF] [LINK]

8. Rose, N. R.; Woon, E. C. Y.; Kingham, G. L.; King, O. N. F.; et.al. Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches. Journal of Medicinal Chemistry, 2010, 53, 1810‑1818.

IF: 5.447  [PDF] [LINK]

7. Inglis, S. R.; Woon, E. C. Y.; Thompson, A. L.; Schofield, C. J. Observations on the deprotection of pinanediol and pinacol boronate esters via fluorinated intermediates. Journal of Organic Chemistry, 2010, 75, 468-471.

IF: 4.450  [PDF] [LINK]

6. Inglis, S. R.; Zervosen, A.; Woon, E. C. Y.; Gerards, T.; Teller, N.; Fischer, D. S.; Luxen, A.; Schofield, C. J. Synthesis and evaluation of 3-(dihydroxyboryl)benzoic acids as D,D-carboxypeptidase R39 inhibitors. Journal of Medicinal Chemistry, 2009, 52, 6097-6106.

IF: 5.447  [PDF] [LINK]

5. Woon, E. C. Y; Arcieri, M.; Wilderspin, A. F.; Malkinson, J. P.; Searcey, M. Solid phase synthesis of chlorofusin analogues as inhibitors of p53/MDM2 interaction. Journal of Organic Chemistry, 2007, 72, 5146-5151.

IF: 4.450  [PDF] [LINK]

4. Woon, E. C. Y; Dhami, A.; Mahon, M. F.; Threadgill, M. D. 3-Substituted-5-nitroisocoumarins from tandem Castro-Stephens coupling- 6-endo-dig cyclisation of 2-iodo-3-nitrobenzoic acid and arylethynes and from ring-closure of methyl 2‑alkynyl-3-nitrobenzoates with electrophiles. Tetrahedron, 2006, 62, 4829-4837.

IF: 3.011  [PDF] [LINK]

3. Woon, E. C. Y; Sunderland, P. T.; Chalkley, D. A.; Threadgill, M. D. Reductive cyclisation of 3-cyanomethyl-3-nitrobenzoates – new approaches to 5‑substituted isoquinolin-1-ones and isoquinolines. Letters in Organic Chemistry, 2006, 3, 619-621.

IF: 0.785  [PDF] [LINK]

2. Woon, E. C. Y; Threadgill, M. D. Ploy(ADP-ribose)polymerase inhibition-where now? Current Medicinal Chemistry, 2005, 12, 2373-2392.                                                          

IF: 4.630  [PDF] [LINK]

1. Wong, S. M.; Shah, B.; Shah, P.; Butt, I. C.; Woon, C. Y.; Wright, J. A.; Thompson, A. S.; Upton, C.; Threadgill, M. D. A new synthesis of “push-pull” naphthalenes by condensation of nitro‑2‑methyl­benzoate esters with dimethylacetamide dimethyl acetal. Tetrahedron Letters, 2002, 43, 2299-2302.

IF: 2.618  [PDF] [LINK]

Patents/ Commercialisation of research

  1. Woon, E. C. Y.; Sun, L. FTO inhibitors as therapeutic compounds.

Patent pending (US Provisional Patent Application No. 1409405.6)

Filed on 28 May 2014.

 

  1. Threadgill, M. D.; Lloyd, M. D.; Thompson, A. S.; Nathubhai, A.; Wood, P. J.; Paine, H. A.; Kumpan, E.; Sunderland, P. T.; Woon, E. C. Y. Tankyrase Inhibitors.

WO 2014087165 A1 (PCT/GB2013/053215)

Filed on 5 December 2013, and issued on 12 June 2014.

First report of highly potent, cell-active and subfamily-selective inhibitors of FTO

This research was featured in the Front Cover Image of Chemical Science, 2015, 6, 112-122. 

[PDF] [Link]

1

Book Chapter: Antiobesity Effects of Natural Products from an Epigenetic Perspective 

Studies in Natural Products Chemistry, volume 41, chapter 6, 161-193.

[PDF] [Link]

2

NUS FoS highlight: Uncovering secrets behind FTO specificity

[LINK]

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Research News

Our work on ‘FTO inhibitors as promising antiobesity drugs’ received national and international media coverage

A patent for this invention has been filed: Provisional Patent Application No. 1409405.6 Filed on 28 May 2014.

 

National News

The Straits Times, 11 Nov 2014, Home, page B5 NUS team’s drug finding could help in obesity fight

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Lianhe Zaobao, 24 Oct 2014, page 9 Local researchers uncover several inhibitors of obesity

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MyPaper, 21 Oct 2014, page B3  New anti-obesity drugs may soon be available

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National Research Foundation website: Scientific Advances Targeting genes to fight the flab

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We are keen to hear from motivated graduate and undergraduate students. You can expect to be intellectually stimulated in this rapidly advancing field of epigenetics. You will benefit from learning a variety of research skills and techniques in a supportive lab environment. There will also be excellent opportunities to interact or work on short attachment with our collaborators from Oxford and Bath. Please contact me if you are interested.

Jobs opportunities

Find out more about the numerous scholarships that are on offer to both Singapore and international students. Undergraduates are welcomed to join us for UROPS study or Final Year Project.

Lets collaborate!

We seek the opportunities to work with scientists from different disciplines, both within and outside of NUS. We are always happy to discuss your research interest and to bring different ideas to your project. Please feel free to get in touch.