Project Details
Project Description
Malaria is a parasitic infection that causes over 200 million cases and over 440,000 deaths each year, with most occurring in children under 5 years of age living in Sub-Saharan Africa. Parasite resistance has now emerged to all current classes of antimalarial drugs, so there is an urgent need to discover and develop new drug classes that target novel parasite pathways in order to avoid cross-resistance with current medicines. Our team will address this challenge using a multidisciplinary approach to discover novel antimalarial compounds, define their mechanisms of action, and optimise their chemical structures to balance potency, selectivity, safety, and pharmacokinetic properties. We will combine our broad expertise and skill-set in parasite biochemistry (including omics and advanced genetic approaches), structural biology, medicinal chemistry and drug design, and drug metabolism, pharmacokinetics and drug delivery to profile early and more advanced hit compounds and determine their suitability for further progression. Our aim is to identify, characterise and progress early lead compounds, which have defined and validated mechanisms of action, defined action on the different parasite stages, demonstrated in vivo efficacy and safety in animal models, and biopharmaceutical properties that are suitable for further development. We will work closely with the Geneva-based Medicines for Malaria Venture (MMV), the leading not-for-profit organisation dedicated to the discovery and development of new antimalarial drugs, to ensure that our programs follow their stringent progression criteria for lead compounds and are well-positioned for advancement into the MMV development portfolio.
| Status | Finished |
|---|---|
| Effective start/end date | 1/01/20 → 31/12/25 |
Funding
- NHMRC - National Health and Medical Research Council (Australia): A$5,000,000.00
Keywords
- malaria
- drug discovery
- drug action
- plasmodium
- parasitic infection
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Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein
Nguyen, W., Boulet, C., Dans, M. G., Loi, K., Jarman, K. E., Watson, G. M., Tham, W. H., Fairhurst, K. J., Yeo, T., Fidock, D. A., Wittlin, S., Chowdury, M., de Koning-Ward, T. F., Chen, G., Yan, D., Charman, S. A., Baud, D., Brand, S., Jackson, P. F. & Cowman, A. F. & 2 others, , 15 Apr 2024, In: European Journal of Medicinal Chemistry. 270, 19 p., 116354.Research output: Contribution to journal › Article › Research › peer-review
Open Access9 Citations (Scopus) -
On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity
Edgar, R. C. S., Malcolm, T. R., Siddiqui, G., Giannangelo, C., Counihan, N. A., Challis, M., Duffy, S., Chowdhury, M., Marfurt, J., Dans, M., Wirjanata, G., Noviyanti, R., Daware, K., Suraweera, C. D., Price, R. N., Wittlin, S., Avery, V. M., Drinkwater, N., Charman, S. A. & Creek, D. J. & 3 others, , 12 Jun 2024, In: mBio. 15, 6, 27 p., e0096624.Research output: Contribution to journal › Article › Research › peer-review
Open Access5 Citations (Scopus) -
Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action
Luo, A. P., Giannangelo, C., Siddiqui, G. & Creek, D. J., 15 Dec 2023, In: Frontiers in Cellular and Infection Microbiology. 13, 12 p., 1308193.Research output: Contribution to journal › Review Article › Research › peer-review
Open Access3 Citations (Scopus)
Equipment
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Australian Translational Medicinal Chemistry Facility (ATMCF)
Stupple, P. (Manager)
Faculty of Pharmacy and Pharmaceutical SciencesFacility/equipment: Facility
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Centre for Drug Candidate Optimisation (CDCO)
Charman, S. (Other)
Pharmacy and Pharmaceutical Sciences Faculty OfficeFacility/equipment: Facility
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Monash Animal Research Platform (MARP)
Findlay, C. (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility