We aim to develop a new class of cholesterol-lowering drugs by blocking the interaction between a protein in the blood called PCSK9 and its receptor, which is implicated in cholesterol absorption. We will do this by designing small stable peptides (mini proteins) that mimic part of the receptor and have the potential to interfere with the normal PCSK9 binding process. These drugs should be less expensive and potentially less immunogenic than competing therapies based on antibodies.
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 Peptide-based Scaffolds For Intracellular Cancer Targets
Funder
National Health and Medical Research Council
Funding Amount
$1,479,836.00
Summary
The overall aim of this project is to develop peptide-based drugs that are able to cross cell membranes and inhibit specific targets inside cells leading to more effective, safer and cost effective drugs for cancer. One potential outcome of the project will be new drug leads to treat melanoma and leukemia that are likely to be less toxic, more potent and less likely to develop resistance than current treatments.
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.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
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.
Repurposing Amiloride Into Breast Cancer Drugs With A Dual-Targeting Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$611,966.00
Summary
This project aims to transform a diuretic drug (amiloride) into a breast cancer drug that acts via a novel molecular mechanism. The science of medicinal chemistry will be used to remove amiloride's diuretic effects whilst gaining potent dual-activity against two breast cancer targets, uPA and NHE1. Our study will validate a new pharmacological approach in cancer treatment and produce patented drugs suitable for development into first-in-class breast cancer drugs.
Reversing Antibiotic Resistance With Efflux Pump Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$494,174.00
Summary
Antibiotic resistance in dangerous pathogens is one of the greatest threats to human health of the 21st century. The main cause of multidrug resistance is the presence of drug efflux pumps, which remove antibiotics from the bacterial cell thereby lowering the antibiotic concentration inside the cells to sub-toxic levels. We will use our expertise on these efflux pumps and on how to inhibit them to develop compounds that could reverse resistance and restore the activity of antibiotics.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Further Development Of The Clinical Potential Of H2 Relaxin
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
The hormone relaxin mediates cardiovascular and kidney changes during pregnancy. These important functions have led to its current use in clinical trials for the treatment of acute heart failure, a condition affecting millions of patients worldwide. However, there is an urgent need for a longer lasting form of relaxin for prolonged treatment of patients. Our studies will focus on understanding the blood breakdown of the peptide to lead to the design of longer lasting relaxin analogues.