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Assistant Professor ANG WEE HAN
B.Sc.(Hons), Imperial College of Science, Technology and Medicine, 1995; Ph.D., Ecole Polytechnique Federale de Lausanne, 2007; NUS Overseas Postdoctoral Fellow, Massachusetts Institute of Technology, 2007- 2009
Contact Information:
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Department of Chemistry, NUS
3 Science Drive 3
Singapore 117543
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Office:
Tel: (65) 6516-5131
Fax: (65) 6779-1691
E-mail: chmawh@nus.edu.sg |
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Research Interests
Inorganic/organometallic and Medicinal Chemistry
My research interest lies in the study and development of metallopharmaceuticals for cancer therapy. This is motivated by the severe limitations faced by current platinum(II) anticancer drugs, including cisplatin and carboplatin, which are still some of the most effective anticancer drugs in clinical use. These problems include their toxic nature and incidence of drug resistance. Some alternative chemotherapeutic strategies of interest that I am looking at include:
a. Functionalized platinum(IV) anticancer compounds. Bis-ammine platinum(IV) compounds belong to an novel class of platinum compounds that can be designed as a pro-drug to cisplatin or other platinum(II) anticancer compounds. They are interesting because they are typically stable at ambient conditions but can be reduced by intracellular biomolecules to release the cytotoxic payload. This strategy has been utilized in the development of satraplatin which is undergoing clinical evaluation as an anticancer drug. I am interested in exploiting this strategy to develop platinum drugs that could overcome drug resistance mechanisms.
b. Ruthenium-based anticancer compounds. Ruthenium has emerged as an attractive alternative to platinum with two ruthenium-based drug candidates undergoing clinical evaluation. Ruthenium drugs are known to be well-tolerated in vivo and have demonstrated high selectivity towards cancer cells in comparison to healthy cells in vitro. I am interested in extending this area of research to develop highly effective ruthenium drugs with low systemic toxicity.
I am also interested in developing techniques to study the interactions of these transition metal-based anticancer drugs with their biological targets. It is often difficult to identify the target of a particular drug, even though it is demonstrated to be highly effective against cancer cells and this is in part due to the complexity of the cellular environment. Building on established genomics and proteomics methodologies, I am working to develop new tools that can be applied not only in the identification of drug targets, but also in the investigation of metal drug-target interactions.
Representative Publications
 WH Ang, I Khalaila, CS Allardyce, L Juillerat-Jeanneret, PJ Dyson, Rational Design of Platinum(IV) Compounds to Overcome Glutathione-S-Transferase Mediated Drug Resistance, J. Am. Chem. Soc., 127, 1382-1383 (2005)
WH Ang, S Pilet, R Scopelliti, F Bussy, L Juillerat-Jeanneret, PJ Dyson, Synthesis and Characterization of Platinum(IV) Anticancer Drugs with Functionalized Aromatic Carboxylate Ligands: Influence of the Ligands on Drug Efficacies and Uptake, J. Med Chem., 48, 8060-8069 (2005)
WH Ang, E Daldini, C Scolaro, R Scopelliti, L Juillerat-Jeanneret, PJ Dyson, Development of Ruthenium Arene Anticancer Drugs that Resist Hydrolysis, Inorg. Chem., 45, 9006-9013 (2006)
WH Ang, PJ Dyson, Classical and Non-classical Ruthenium-based Anticancer Drugs: Towards Targeted Chemotherapy (review), Eur. J. Inorg. Chem., 20, 4003-4018 (2006)
A Dorcier, WH Ang, S Bolano, L Gonsalvi, L Juillerat-Jeannerat, G Laurenczy, M Peruzzini, AD Phillips, F Zanobini, PJ Dyson, In Vitro Evaluation of Rhodium and Osmium RAPTA Analogues: the Case for Organometallic Anticancer Drugs not Based on Ruthenium, Organometallics, 25, 4090-4096 (2006)
CA Vock, WH Ang, C Scolaro, L Juillerat-Jeanneret, G Sava, PJ Dyson, Synthesis, Characterisation and In Vitro Evaluation of Novel Ruthenium(II) h6-arene Complexes with MDR Modulators as Ligands, J. Med. Chem., 50, 2166-2175 (2007)
A Casini, G Mastrobuoni, WH Ang, C Gabbiani, G Pieraccini, G Moneti, PJ Dyson, L Messori, ESI‑MS Characterization of Protein Adducts of Anticancer Ruthenium(II)-Arene PTA (RAPTA) Complexes, ChemMedChem, 2, 631-635 (2007)
C Hartinger, WH Ang, A Casini, L Messori, BK Keppler, PJ Dyson, Mass Spectrometric Analysis of Ubiquitin-Platinum Complex interaction in Leading Anticancer Drugs: MALDI versus ESI, J. Anal. At. Spectrom., Metallomics Special Issue (2007)
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