Professor Shudong Wang
|Position:||Professor of Medicinal Chemistry|
|Division/Portfolio:||Division of Health Sciences|
|School/Unit:||School of Pharmacy and Medical Sciences|
|Campus:||City East Campus|
|Telephone:||+61 8 830 22372|
|URL for Business Card:||http://people.unisa.edu.au/Shudong.Wang|
Professor Shudong Wang’s research focuses on drug discovery in several therapeutic areas, especially cancer. She is particularly interested in forging multidisciplinary approaches for drug discovery translational research.
After received her Ph.D. in 1998 Shudong spent seven years in a British pharmaceutical company (Cyclacel Inc., NASDAQGM:CYCC). As head of Chemistry and programme manager (2000-2005) she helped to establish medicinal chemistry and drug discovery capability of the company. She played a leading role in several projects that reached preclinical and clinical stages.
In 2005, Shudong joined in University of Nottingham as Reader in Medicinal Chemistry at School of Pharmacy, the top pharmacy school in the United Kingdom. During the six year (2005-2011) she has built up a strong multi-disciplinary team, composed of medicinal chemistry, biology and pharmacology, which has enabled her team to conduct world-class drug discovery research. Several kinase inhibitor drug leads reached the late preclinical stage.
In December 2011 Professor Wang relocated to the University of South Australia. As Chair in Medicinal Chemistry at School of Pharmacy and Medical Sciences, she has been leading to establish drug discovery and cancer research capabilities. Her research activities at the UniSA are directed towards developing new drug leads for targeted cancer therapy. These involve structure- and target-guided design and synthesis of compound libraries that are used to characterise the cellular consequences associated with the diseases. The strategy holds promise for rapid advancement of drug discovery in an effort to identify both drug candidates and novel therapeutic targets.
Despite having spent many years in industry, Professor Wang has a strong track record of publication and is a nominated inventor on over 75 patent applications. Her research profile has led to a number of collaborations with world-class research teams in UK, USA, Hong Kong and China. She holds visiting Professorships to the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Sun Yat-Sen University of China. She was scientific consult to several companies and has established strong links with several international drug companies.
• Royal Society of Chemistry (Fellow; FRSC)
• Royal Australian Chemical Institute (Chartered Chemist; MRACI CChem)
• American Association for Cancer Research (Member)
• American Chemical Society (Member)
- Professor Wang current research is focussed on the discovery and development of novel protein kinase inhibitor drugs in various therapeutic areas particular cancer. The current ongoing research programmes include:
- • Pre-clinic evaluation of mitotic kinase inhibitors for cancer therapy. A diverse library of drug-like inhibitors that effectively block the activity of mitotic kinases and induce cancer cell apoptosis has been developed. The drug candidate compounds possessing excellent pharmaceutical properties have been identified and are currently being evaluating for their in vivo anti-tumour efficacy and preclinical safety profiles. We will complete the candidate selection and pre-clinic evaluation in a short period of time. The effective drug candidate will be developed as a novel cell-cycle agent for cancer therapy.
- • Discovery of Mnk pharmacologic inhibitors for targeted cancer therapy. Elevated expression level of eIF4E promotes cancer development and progression. Activity of eIF4E is modulated through phosphorylation by Mnk1 and Mnk2 and the phosphorylation event is necessary for oncogenic transformation. Importantly, recent findings suggest that Mnks are dispensable for normal development. For these reasons, pharmacologic inhibitors of Mnks may provide a nontoxic and effective anti-cancer therapeutic strategy. This project aims to identify novel and selective Mnk inhibitors for target validation and clinical application.
- • Development of Pim1 inhibitors for treatment of hematopoietic malignancies. Pim1 is a proto-oncogene that has been implicated in early transformation and tumour progression, especially in hematopoietic malignancies and prostate carcinoma where it is a marker of a poor prognosis. Therefore Pim1 is emerging as an important target in drug discovery. However the current challenge is to obtain compounds that specifically inhibit only Pim1. This project provides a novel class of selective Pm1 inhibitors as potential therapeutic agents which are also used to investigate the different roles of other members of Pim kinase family in cells.
T.Teo, M.Yu, Y. Yang, T. Gillam, F. Lam, M.J. Sykes, and S. Wang. Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis chronic myeloid leukemia cells. Cancer Letters, DOI.10.1016/j.canlet.2014.12.029, 2014.
B.T. Le, M. Kumarasiri, J. R. J. Adams, M. Yu, R. Milne, M. J. Sykes and S. Wang. Targeting Pim kinases for cancer treatment: opportunities and challenges. Future Medicinal Chemistry, 2014, in press.
M. Kumarasiri, T. Teo, and S. Wang. Dynamical Insights of Mnk2 Kinase Activation by Phosphorylation to Facilitate Targeted-Inhibitor Discovery. Future Medicinal Chemistry, 2014, in press.
Lu, T., Laughton, C.A., Wang, S., Bradshaw, T.D.,In vitro Anti-tumour Mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide. Mol Pharmacol, pii: mol.114.093245, 2014.
F. Lam, A.Y. Abbas, H. Shao, T. Teo, J. Adams, P. Li, T.D. Bradshaw, P.M. Fischer, E. Walsby, C.Pepper, Y. Chen, J. Ding and S. Wang. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget, Vol. 5, No. 17, 2014.
S. Diab, M. Kumarasiri, M. Yu, T. Teo, C. Proud, R. Milne, and S. Wang. MAP Kinase-interacting kinases: emerging targets against cancer. Chemistry & Biology, 21, 441-452, DOI:10.1016/j.chembiol.2014.01.011, 2014.
T. Lu, A. Goh, M. Yu, J. Adams, F. Lam, T. Teo, P. Li, B. Noll, L. Zhong, S. Diab, O. Chahrour, A. Hu, A. Y. Abbas, X. Liu, S. Huang, C. J. Sumby, R. Milne, C. Midgley, and S. Wang. (2014) Discovery of (E)-3-((styrylsulfonyl)methyl)pyridine and (E)-2-((styrylsulfonyl)methyl)pyridine derivatives as anti-cancer agents: synthesis, structure-activity relationships, and biological activities. Journal of Medicinal Chemistry,57, 2275-2291, dx.doi.org/10.1021/jm4019614, 2014.
S. Diab, T. Teo, M. Kumarasiri, P. Li, M.Yu, F. Lam, S. Basnet, M. J. Sykes, H. Albrecht, R. Milne, and S. Wang. Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk inhibitors: synthesis, SAR analysis and biological evaluation. ChemMedChem, DOI:10.1002/cmdc.201300552, 2014
Elisabeth Walsby, Guy Pratt, Hao Shao, Abdullah Y. Abbas, Peter M. Fischer,Tracey D. Bradshaw, Paul Brennan, Chris Fegan, Shudong Wang, and Chris Pepper. A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine. Oncotarget, DOI:1568 [pii],2013.
Hao Shao, Shenhua Shi, David W. Foley, Frankie Lam, Abdullah Y. Abbas, Xiangrui Liu, Shiliang Huang, Xiangrui Jiang, Nadiah Baharin, Peter M. Fischer, and Shudong Wang. Synthesis, structure-activity relationship and biological evaluation of 2,4,5-trisubstituted pyrimidine CDK inhibitors as potential anti-tumour agents. European Journal of Medicinal Chemistry, 10.1016/j.ejmech.2013.08.052, 2013.
Jinqiang Hou, Theodosia Teo, Matthew J. Sykes, and Shudong Wang. Insights into the Importance of DFD-Motif and Insertion I1 in Stabilizing the DFD-Out Conformation of Mnk2 Kinase. ACS Medicinal Chemistry Letters, dx.doi.org/10.1021/ml400145x, 2013.
Shao, H., Shi, S., Huang, S., Hole, A., Abbas, A. Y., Baumli, S., Liu, X., Lam, F., Foley, D. W., Fischer, P. M., Noble, M., Endicott, J. A., Pepper, C., Wang, S., Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: synthesis, x-ray crystal structures, SAR and anti-cancer activities. Journal of Medicinal Chemistry. DIO:10.1021/jm301475f, 2013.
Wang S., and Shao, H. Therapeutic compounds, WO2013156708A1, 2013.
Hole, A., Baumli, S., Shao, H., Shi, S., Pepper, C., Fischer, P. M., Wang, S., Endicott, J. A., Noble, M., Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity. Journal of Medicinal Chemistry. DOI:10.1021/jm301495v, 2013.
P.M. Lukasik, S. Elabar, F. Lam, H. Shao, X. Liu, A.Y. Abbas and S. Wang. Synthesis and biological evaluation of imidazo[4,5-b]pyridine and 4-heteroarylpyrimidine derivatives as anti-cancer agents. Eur Journal of Medicinal Chemistry, 57, 311-322, 2012.
J. Hou, F. Lam, C Proud and S. Wang. Targeting Mnks for Cancer Therapy. Oncotarget, 3(2):118-31, 2012
H.M. Alkahtani, A. Y. Abbas and S. Wang. Synthesis and biological evaluation of benzo[d]imidazole derivatives as potential anti-cancer agents. Bioorg. Med. Chem. Lett. 22(3):1317-21, 2012.
X. Liu, S. Shi, F. Lam, C. Pepper, P.M. Fischer, and S. Wang. CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared with flavopiridol. International Journal of Cancer, 130(5):1216-26, 2012.
X. Liu, F. Lam, S. Shi, P.M. Fischer, S. Wang. In vitro antitumor mechanism of a novel cyclin-dependent kinase inhibitor CDKI-83. Invest. New Drugs. 30(3):889-97, 2012.
Lam F., Bradshaw T.D., Mao H.,Roberts S., Pan Y. and Wang S. ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities. Invest New Drugs. DOI 10.1007/s10637-011-9755-9, 2011.
Wang S., O. Chahrour, T Lu and A. Hu. Compounds for treating proliferative diseases. WO2011/161446, 2011.
Chahrour, A. Abdalla, F. Lam, C. Midgley, and S. Wang. Synthesis and biological evaluation of benzylstyrylsulfonyl derivatives as potent anticancer mitotic inhibitors, Bioorg. Med. Chem. Lett.. 21(10):3066-9, 2011.
Z Xu,Z Liu, T Chen, T Chen, Z Wang, G Tian, J Shi, X Wang, X Lu, X Yan, G Wang, H Jiang, K Chen, S Wang, Y Xu, J Shen, W Zhu. Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors. J. Med. Chem. 54, 5607–5611, 2011.
Wang S., S. Shi, A. Zaytsev, Fischer, P.M., Pyrimidines, triazines and their use as pharmaceutical agents. US201109249, 2011.
Wang S., O. Chahrour, T Lu and A. Hu. Compounds for treating proliferative diseases. WO2011/161446, 2011.
Wang S., S. Shi, A. Zaytsev, Fischer, P.M., Pyrimidines, triazines and their use as pharmaceutical agents, University of Nottingham, CN102143953, 2011.
S Wang, C Meades, G Wood, J O'boyle, C Mcinnes, P M Fischer. Pyrimidine compounds. US7897605, 2011.
S Wang, G Wood, K Duncan, C Meades, D Gibson, J Mclachlan , A Perry , D Blake , D Zheleva, P M Fischer. Pyrimidin-4-yl-3, 4-thione compounds and their use in therapy. US7902361, 2011.
S. Wang, C. Midgley, F. Scaërou, J. Grabarek, G. Griffiths, W. Jackson, G. Kontopidis, S.J. McClue, C. McInnes, C. Meades, M. Mezna, A. Plater, I. Stuart, M.P. Thomas, G. Wood, R. Clark, D. Blake , D.I.Zheleva, D.P. Lane, R.C. Jackson, D.M. Glover, P.M. Fischer. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine Aurora Kinase Inhibitors. Journal of Medicinal Chemistry, 53, 4367–4378, 2010.
S. Wang, G. Griffiths, C.A. Midgley, A.L. Barnett, M. Cooper, J. Grabarek, L. Ingram, W. Jackson, G. Kontopidis, S.J. McClue, C. McInnes, J. McLachlan, C. Meades, M. Mezna, I. Stuart, M.P. Thomas, D.I.Zheleva, D.P. Lane, R.C. Jackson, D.M. Glover, D.G. Blake, P.M. Fischer. Discovery and Characterisation of 2-Anilino-4-(thiazol-5-yl)pyrimidine Transcriptional CDK Inhibitors as Anticancer Agents. Chemistry & Biology, 17, 1111-1121, 2010.
N.A. McIntyre, C. McInnes, G. Griffiths, A.L. Barnett, G. Kontopidis, A.M.Z. Slawin, W. Jackson, M.Thomas, D.I. Zheleva, S. Wang, D.G. Blake, N.J. Westwood, P.M. Fischer. Design, Synthesis and Evaluation of 2-Methyl- and 2-Amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as Ring-Constrained 2-Anilino-4-(thiazol-5-yl)pyrimidine Cyclin-Dependent Kinase Inhibitors. Journal of Medicinal Chemistry, 53, 2136–2145, 2010.
C Mcinnes, M P Thomas, S Wang, N Mcintyre, N Westwood, P M Fischer. Thiazolo-, oxazalo and imidazolo-quinazoline compounds capable of inhibiting protein kinases. US7576091, 2010.
S. He, J. Yang, B. Wu, Y. Pan, H. Wan, Y. Wang, Y. Du, S. Wang. Neuroprotective Effect of Parthenocissin A, A Natural Antioxidant and Free Radical Scavenger, in Focal Cerebral Ischemia of Rats. Phytother. Res. 24, 63–70, 2009.
E. A. Taha, N. Salamaa and S. Wang. Enantioseparation of cetirizine by chromatographic methods and discrimination by 1H-NMR, Drug Testing and Analysis,1(3);118, 2009.
S Wang. Pyrimidine compounds. CN100519553, 2009.
N. Salama and S. Wang. Quantitative Mass Spectrometric Analysis of Ropivacaine and Bupivacaine in Authentic, Pharmaceutical and Spiked Human Plasma without Chromatographic Separation, Analytical Chemistry Insights. 4:11, 2009.
E. A. Taha, N. Salama and S. Wang. Micelle Enhanced Fluorimetric and Thin Layer Chromatography Densitometric Methods for the Determination of (±)Citalopram and its Enantiomer Escitalopram. Analytical Chemistry Insight. 4:1, 2009.
Wang S., S. Shi, A. Zaytsev, Fischer, P.M., Pyrimidines, triazines and their use as pharmaceutical agents. WO2009/118567, 2009
S. Wang, and P.M. Fischer. Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology, TRENDS in Pharmacological Sciences. 302–313, 2008.
S Wang, C Meades, A Osnowski, G Wood, P M Fischer. US7388015, 2008.
Kontopidis, G., McInnes, C., Pandalaneni, S.R., McNae, I., Gibson, D., Mezna, M., Thomas, M., Wood, G., Wang, S., Walkinshaw, M.D., and Fischer, P.M. Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design. Chemistry & Biology. 13:20, 2006.
Wang, S., Zhelev, N.Z., Duff, S., and Fischer, P.M. Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin", Bioorg. & Med. Chem. Lett.. 16:2628, 2006.
Wang S., Meades C., Wood G., Osnowski A., Anderson S., Yuill R., Thomas M., Mezna M., Jackson W., Midgley C., Griffiths G., Fleming I., Green S., McNae I., Wu S.Y., McInnes C., Zheleva D., Walkinshaw M.D., Fischer P.M. 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity. J. Med. Chem., 47:1662, 2004.
S. Wang, G. Wood, C. Meades, G. Griffiths, C. Midgley, I. McNae, C. McInnes, S. Anderson, W. Jackson, M. Mezna, R. Yuill, M. Walkinshaw and P. M Fischer. Synthesis and Biological Activity of 2-Anilino-4-(1H-pyrrol-3-yl)pyrimidine CDK Inhibitors. Bioorg. & Med. Chem. Lett. 14: 4237, 2004.
McInnes C., Wang S., Anderson S., O'Boyle J., Jackson W., Kontopidis G., Meades C., Mezna M., Thomas M., Wood G., Lane D.P., Fischer P.M. Structural determinants of CDK4 inhibition and design of selective ATP competitive inhibitors. Chemistry & Biology, 11:525, 2004.
Wang S., Wood G., Meades C., Griffiths G., Midgley C., Grabarek J., Cooper M., Anderson S., Jackson W., Yuill R., McNae I., McInnes C., Zheleva D., Walkinshaw M., Lane D.P., Jackson R., Fischer P.M. Discovery of 2-phenylamino-4-(pyrrol-3-yl)-pyrimidines new class of CDK inhibitors: synthesis, crystal structures, in vitro anti-proliferative activity and biochemical evaluation. Clin. Cancer Res. 9:61, 2003.
Šarek J., Klinot J., Džubák P., Klinotová E., Nosková V., Krecek V., Korínková G., Thomson J.O., Janoštáková A., Wang S., Parsons S., Fischer P.M., Zhelev N.Z., Hajdúch M. New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships. J. Med. Chem. 46:5402, 2003.
McClue S.J., Blake B., Clarke R., Cowan A., Cummings L., Fischer P., Mackenzine M., Melvile J., Steward K., Wang S., Zhelev N., Zheleva D. and Lane D. In vitro and in vivo antitumour prosperities of the cyclin dependent kinase inhibitor CYC202 (R-Roscovitine). Int. J. Cancer, 102:463, 2002.
Wang S., Clarke R., Jackson W., Lyon C.E., McClue S., McInnes C., Westwood R., Walkinshaw M., Lane D.P. Fischer P.M., Structure-based design and optimisation of substituted 2-phenylamino-4-(thiazol-5-yl)-pyrimidine CDK inhibitors. Eur. J. Cancer, 38:124, 2002.
Wang S., McClue S.J., Ferguson J.R., Hull J.D., Stokes S., Parsons S., Westwood R., Fischer P.M. Synthesis and configuration of the cyclin-dependent kinase inhibitor roscovitine and its enantiomer. Tetrahedron:Asymmetry, 12 (20):289, 2001.
Fischer P. M, Zhelev N. Z., Wang S., Melville J. Fahraeus R., Lane D. P. Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector penatratin, J. Peptide Res. 55:163, 2000.
Warrener R.N.; Wang S., Russell R.A. The synthesis of U-shaped cavity molecules with inner-surface functionality. Tetrahedron. 53:3975, 1997.
Warrener, R., Wang, S., Russell, R. and Gunter, M. Novel Crown Ether Assemblies: The Role of Isobenxofurans for Attaching Crown Ethers to Rigid Molecular Racks in Geometrically Precise Fashion. Synlett, 1:47-50, 1997.
Warrener, R., Shultz, A., Butler, D., Wang, S., Mahadevan, I. and Russell, R. A New Building BLOCK Technique Based on Cycloaddition Chemistry for the Regiospecific Linking of Alicyclic Sub-Units as a Route to Large, Custom-Fuctionalised Structures. Chemical Communications. 1023-1024, 1997.
Warrener, R., Wang, S. and Russell, R. The Synthesis of U-Shaped Cavity Molecules with "Inner Surface" Functionality, Tetrahedron, 53:3975-3990, 1997.
Warrener, R., Wang, S., Butler, D. and Russell, R. The Design of Inner-Functionalised U-Shaped Cavity Molecules: Role of Phenyl Subtituents 1,3-Position Isobenzofurans and Oxa-Bridges in the Dienophile as Stereochemical Controlling Elements, Synlett, 1:44-46, 1997.
We use a structure-guided approach to design novel classes of drug-like molecules which target the respective kinases with high potency and specificity. The inhibitor compounds are evaluated for anti-cancer efficacy, ADME/Tox and pharmaceutical properties and for clinic development.
All PhD projects I am offering are highly multidisciplinary. Students will be provided comprehensive training in the areas of structure guided drug design, medicinal chemistry, cancer biology, pharmacology, pharmaceutical sciences and modern drug discovery & development.
- Development of Pim1 Inhibitors for Treatment of Hematopoietic Malignancies.
|In this program students will design inhibitors using structural guided approach. Compounds will be synthesised and tested in our biochemical & cell-based screening cascade. Drug-likeness and therapeutic applications of drug candidate compounds will be evaluated in disease models.|
This PhD program is highly multidisciplinary. Students will be provided comprehensive training in the areas of structural guided & computer aided drug design, synthetic and medicinal chemistries and modern drug discovery & development.
|In this program we aim to design inhibitors focusing their specificity by structural guided approach. Novel classes of small molecular inhibitors will be developed using our advanced medicinal chemistry and biochemical & cell-based screening cascade. Drug-likeness of compounds will be evaluated in vitro and in vivo disease models.|
PhD Students will be provided comprehensive training in the areas of structural guided & computer aided drug design, synthetic and medicinal chemistries and modern drug discovery & development.
|This project aims to evaluate a novel class of PLK1 inhibitors as potential anti-cancer agent. The compounds potency, selectivity and toxicity will be evaluated. The detailed cellular mode of action of lead compounds will be evaluated. The anti-tumour efficacy will be assessed in in vivo models. Drug candidate compounds for clinic devlopment will be chosen based on their efficacy and ADME/PK properties. |
This project will provide comprehensive training and research opportunity in the areas of cancer biology, pharmacology, pharmaceutical sciences and modern drug discovery.
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