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Novel Approaches To The Targeting Of GPCRs Towards Improved Treatment Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The focus of these studies are two important types of brain proteins that have been implicated in various symptoms associated with schizophrenia. The aim is to exploit two emerging paradigms of drug action at these brain proteins that will allow us to target them in a more selective manner. In particular, these studies will provide a starting point for safer, more effective treatments for schizophrenia.
Rational Co-targeting Of G Protein-coupled Receptors As A Novel Approach Towards Treating Neuropsychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
Schizophrenia is a common mental disorder with multiple symptoms. Current therapeutics only treat some of these symptoms. This project will focus on two important brain proteins implicated in schizophrenia. With the hypothesis that the rational targeting of these two proteins will lead to the design of more effective medicines for treatment of schizophrenia we will develop novel methods to selectively and simultaneously and target these two proteins.
Investigating The Impact Of Coincident Modulation Of Adenosine And Glutamate Receptors On Neuronal Activity – Implications For CNS Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Dementia in particular Alzheimer's disease, is one of the leading causes of death. There remains a need for new drugs to treat both symptoms and disease progression. Two receptors in the brain, the adenosine A1 (A1AR) and metabotropic glutamate 5 (mGlu5) are suggested to be promising new drug targets for dementia. In order to better develop drugs that target these receptors, we will develop a better understanding of activity of these receptors under conditions of health and disease.
Understanding Novel Drug Binding Pockets At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$425,538.00
Summary
Cell-surface proteins exhibit multiple secondary binding sites for which only synthetic drugs have been identified so far. My hypothesis is that these secondary binding sites are common to most proteins because they are primarily targeted by largely yet unidentified endogenously released molecules that can modify the biology of these proteins.
This research will push the boundaries of current knowledge in receptor pharmacology and translate this knowledge into clinical outcomes. Receptors are proteins on the surface of our cells that bind hormones, neurotransmitters and pharmaceuticals. By better understanding the complexities of how these receptors work at the molecular level, the objective is to develop improved treatments and better clinical management for a range of medical conditions.
Adenosine Receptor Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$682,163.00
Summary
Adenosine A1 receptor (A1R) activation confers powerful protection to heart cells, however clinical application remains suboptimal due to adverse effects such as a slowing in heart rate and decrease in blood pressure. Importantly a new class of compounds, A1R biased agonists, can mediate potent cardioprotection in the absence of adverse effects. This proposal will establish the molecular mechanisms involved and the scope to develop A1R biased agonists as a novel approach to treat heart disease.
Adenosine Receptor Context-Specific Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,021,744.00
Summary
Heart attacks and secondary heart failure remain significant health burdens. Stimulation of adenosine receptors located on heart cells confers powerful cardiac protection, improving acute and longer-term heart function subsequent to a heart attack but avoiding the usual unwanted effects from this approach. We aim to better understand the mechanism of action of potential adenosine receptor therapeutics and establish the clinical potential of these compounds using animal models of heart failure.
Understanding Mechanisms Of Allostery And Biased Agonism At The Adenosine A1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$603,033.00
Summary
This project focuses on an important protein found in the heart. Drugs that activate this protein can protect the heart against damage that occurs after a heart attack, but they all have undesirable side effects. We have discovered a new class of molecule that can protect the heart without these side effects. We now seek to understand how these compounds work at the molecular level. This knowledge can facilitate the design of safer medicines for the treatment of cardiovascular disease.
Bitopic Ligands As A Novel Approach To G-protein-coupled Receptor Selectivity
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
This project will focus on two important types of brain proteins that have been implicated in various symptoms associated with schizophrenia. The aim is to exploit a new paradigm of drug action that we have discovered, whereby novel compounds can be utilized to simultaneously target multiples sites on these brain proteins, in an effort to discover new mechanisms that can promote more selective signalling and, ultimately, can be used to design safer and more effective medicines.
A New Therapeutic Target For Stress-related Relapse
Funder
National Health and Medical Research Council
Funding Amount
$685,266.00
Summary
Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. We have identified a novel system in the brain for the regulation of stress-induced relapse. Successful completion of this project will indicate improved pharmacotherapeutic strategies for the treatment of alcoholism and drug abuse. Given the scale and costs of substance abuse disorders, improved therapeutic approaches will have immediate and sustained impact.