Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
Development Of Fragment Hits Into Effective Antimalarials; Targeting Malaria Eradication
Funder
National Health and Medical Research Council
Funding Amount
$676,798.00
Summary
We have used a novel method that samples the diversity of natural products with a small sub-set of compounds, and observed direct interaction between these compounds and proteins important in the malaria parasite life cycle. This project will develop these identified active compounds towards the goal of producing a drug to fight stages of the malaria parasite’s life cycle that are not targeted by currently available antimalarial drugs.
Small Molecule Therapeutics: From Infectious And Parasitic Diseases To Cancers
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
I will lead a team of medicinal chemists to discover better treatments of diseases focused in two major domains. On one hand, I will discover new drugs to treat certain parasitic diseases such as Sleeping Sickness, Chagas disease and malaria, all caused by protozoal parasites. On the other hand, I will discover new drugs to treat certain cancers, in particular acute myeloid leukemia and Burkitt’s lymphoma, caused by dysfunction of certain types of enzymes called histone acetyltransferases.
Development Of Small Molecule Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$621,558.00
Summary
Cancers rely on the deregulation of key cellular pathways. Along with biological and genetic tools, small molecules are powerful probes to understand these mechanisms. During the course of this research program, we will develop new and drug-like molecules that reinstate the cell death process to combat malignancies. This research will bring important advances for potential chemotherapies and create probes to better understand the biology of programmed cell death processes.
Development Of Small Molecule Antagonists Of HGF/SF And MET Signalling To Treat Metastatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$353,866.00
Summary
The spread of cancer throughout the body, metastasis, is the major cause of death from cancer. The MET receptor plays a crucial role in over 60% of all metastases and several approaches to block its activity are currently in clinical trials. This project will use a new approach to develop small molecule inhibitors that block the MET receptor from interacting with another protein, HGF/SF. Small molecules that block this interaction will be highly effective treatments against metastatic cancers.
Unique And Selective Small Molecules To Dissect Histone Acetyltransferase Biology
Funder
National Health and Medical Research Council
Funding Amount
$694,255.00
Summary
A class of enzymes called histone acetyltransferases appear to be important in a variety of diseases, from inflammation to cancer. We are developing potent and selective compounds that will be able to tell us which of these enzymes may be targets for cancer, and which for inflammatory disorders. This will be invaluable for better treatment of debilitating human diseases with unmet needs.
Development Of Antimalarial Histone Deacetylase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$573,676.00
Summary
Human histone deacetylases (HDACs) are enzymes clinically validated as targets for cancer chemotherapy. Different HDAC enzymes are important for survival of infectious organisms, such as protozoan Plasmodium parasites that cause malaria. This project will develop promising drug leads that kill the parasites without damaging human cells through preclinical studies in mice towards a future clinical trial for the treatment of malaria in humans.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
Development Of Reversible Inhibitors Of Factor XIa
Funder
National Health and Medical Research Council
Funding Amount
$444,318.00
Summary
Blood usually clots in response to injury, but unwanted clots can cause thrombosis, as well as leading to stroke and heart disease. Existing drugs to treat thrombosis suffer from drawbacks such as invasive monitoring, interaction with diet and other medicines, and bleeding complications. New drugs are clearly needed. Our expert group of researchers will discover new anti-thrombotic compounds based upon our previous identification of natural products with anticoagulant properties.
Development Of Potent And Selective Blockers Of Acid Sensing Ion Channels For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$578,704.00
Summary
More than three million Australians suffer from chronic pain, and there are few effective drugs available for treating this condition. A 2007 Access Economics Report estimated the economic burden of chronic pain in Australia at $34.3 billion. Acid-sensing ion channels (ASICs) are a recently discovered family of proteins that play a key role in sensing pain. The goal of this project is to develop potent blockers of these channels that can be used to treat patients suffering from persistent pain.