Pharmacology Of Potential Anti-Tumour Agents: Iron And Copper Chelators Of The ApT, BpT And DpT Classes
Funder
National Health and Medical Research Council
Funding Amount
$647,137.00
Summary
Cancer cells take up more of the essential nutrients copper and iron than normal cells. Increased metabolism of these metals is linked to tumour growth progression. Our laboratory has developed compounds that bind these metals in tumours. Our studies suggest our novel compounds display a novel tumour targeting strategy which may explain their ability to also overcome drug resistance. This unique mechanism of action is crucial to understand for the development of novel anti-cancer agents.
Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
Resistance To Herceptin (trastuzumab) In HER2 Positive Breast Cancers: The Role Of Calcium Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$620,292.00
Summary
The monoclonal antibody therapy trastuzumab has revolutionized the treatment of women with Her2 positive breast cancer. Unfortunately some Her2 positive breast cancers do not respond to this therapy or gradually develop resistance. This project will define how an important cellular signal is remodeled in breast cancers resistant to trastuzumab. The ability of modulators of this signaling pathway to alter the sensitivity of breast cancers to trastuzumab will also be determined.
Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
Calcium Signaling And Epithelial-mesenchymal Transition: A New Approach To Identifying Pharmacological Targets For Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$561,645.00
Summary
The largest killer of women with breast cancer is disease that has spread e.g. to brain, bones, lungs. Once breast cancer has spread in this way to secondary sites, also known as metastatic disease, then there is limited treatment available and generally therapy is palliative only. Our work describes experiments that will help us understand the process of metastasis and provide new avenues for drug discovery in metastatic disease, thus helping women who have a poor prognosis.
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.
Exploiting The Pharmacokinetic And Pharmacodynamic Properties Of Bile Acid Receptor Agonists To Treat Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$653,952.00
Summary
We have generated preliminary data suggesting that chemicals made by the liver, called bile acids, act on fat cells to release a hormone called adiponectin. In liver disease adiponectin has favorable effects, including reducing liver inflammation and fibrosis (scarring). By using drugs that mimic the action of bile acids we expect that adiponectin production by fat cells can be increased, creating a new way to treat patients with chronic liver diseases.
A Randomised Controlled Trial Of Deprescribing To Optimise Medical Therapy For Frail Older People: The Opti-Med Study.
Funder
National Health and Medical Research Council
Funding Amount
$1,444,996.00
Summary
Many older people living in residential aged care facilities (RACF) are prescribed medications of uncertain benefit. The primary aim of the Opti-med study is to determine the safety and benefits of reducing the number of medications prescribed to frail older people in RACF. We will withdraw as many medications as possible from participants in the intervention group. Our study will provide randomised controlled data on the safety and efficacy of ceasing medications in frail older people.
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.
Dynamic Action Potential Clamp Studies Of Drugs That Affect The Cardiac Action Potential
Funder
National Health and Medical Research Council
Funding Amount
$343,976.00
Summary
The development of drugs to treat and.or prevent cardiac arrhythmias have been plagued by the side-effect of actually increasing the risk of sudden death. One of the reasons for this is that drugs that work well in one part of the heart may cause problems in another part. We are developing a system called “dynamic action potential clamp” that will make it easier for researchers to assess the effect of drugs in different regions of both normal and diseased hearts.