Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
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.
Downsizing A Human Protein To Modulate Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$516,793.00
Summary
We have discovered how to downsize a human protein to very small molecules with the same activities and potencies. Small changes enable the compounds to powerfully block the actions of the protein. These small molecules are very stable in blood, whereas the protein deactivates in minutes. This project will develop the small molecules into experimental drugs and test them in human cells and proteins, and in rats to evaluate their potential for treating human inflammatory diseases.
Venoms To Drugs: Translating Venom Peptides Into Human Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Many disorders of the nervous system, including chronic pain, epilepsy and the neuronal degeneration suffered following a stroke, result from malfunction of channels that ferry ions across neuronal cell membranes. There are very few drugs available for treating these disorders and they often have debilitating side-effects. We are developing potent and selective modulators of these ion channels as the next-generation of safe and effective analgesic, anti-epileptic, and neuroprotective drugs.
Modulation Of Feeding Through Pharmacological Targeting Of The Relaxin-3 Receptor RXFP3
Funder
National Health and Medical Research Council
Funding Amount
$584,955.00
Summary
Relaxin-3 is a neuropeptide that regulates a number of physiological processes, including food intake, suggesting that the relaxin-3 receptor RXFP3 may be a new target for treatment of eating disorders such as obesity. This project will develop new selective and high-affinity ligands for RXFP3, which will be critical pharmacological tools for the preclinical studies and evaluation of this system.
Understanding The Structure/function Relationships Of The Iron Regulatory Peptide Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
This project seeks to understand the interactions between the peptide hormone hepcidin and its receptor and use this information to develop new drugs. Hepcidin is the major iron-regulatory hormone in humans and a range of iron-related diseases are caused by incorrect levels of this hormone. Many Australians are affected by these diseases so the development of hepcidin-based treatments has the potential to have significant impact on the overall health of the community.
Improving Synthetic Methodology To Prepare Pre-clinical Analogues Of Human Insulin
Funder
National Health and Medical Research Council
Funding Amount
$457,708.00
Summary
The glucose regulatory hormone, insulin, remains the only treatment for type I diabetes and up to 30% of type II diabetes, both of which are among the world’s fastest growing chronic diseases today. Because insulin, if taken orally, would be broken down quickly, it has usually been given by injection. This project will develop novel chemical methods for the efficient preparation of novel insulin therapeutics with improved stability and oral bioavailability for prolonged treatment of patients.
Next Generation Relaxin Molecular Probes And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
The peptide hormone relaxin is poised to be the first new treatment for acute heart failure in more than 40 years. However, like other therapeutic peptides, it has a very short duration of action due to its rapid clearance by the body. My work will utilize powerful medicinal chemistry methods to develop new analogues of relaxin that have much longer action by complexing it with sugar or making relaxin polymers. I will also produce smaller relaxin analogues that will be cheaper to manufacture.
Chronic pain from damage to the nervous system is extremely debilitating and notoriously difficult to treat. The current drug of choice, gabapentin, has serious side effects and only works in two-thirds of patients. We have developed a drug, derived from sea snail venom, that exhibits ten times the activity of gabapentin. This proposal seeks to progress our drug to clinical trials and attract a commercial partner for its development into the market.