Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less
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.
Pharmacological Inhibitors Of Mnk For The Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,894.00
Summary
Cancer is a leading cause of death worldwide. In 2010 an estimated 43,000 Australians died from cancer and 114,000 new cases were diagnosed. New treatments are urgently needed. Protein kinases Mnks promote human tumourogenesis, but they are dispensable for normal tissue development. Inhibition of Mnks’ activity therefore presents an excellent strategy for effective and nontoxic cancer therapy. This project aims to develop Mnk inhibitor drug candidates for potential clinic application.
Validation Of Formyl Peptide Receptor (FPR)2 As A Target For New Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$588,529.00
Summary
Treatment of breast and other cancers is making incremental improvements, but premature death from this disease and its recurrence in some women after a long period of remission are not adequately treated by current drugs. New work has identified a target called FPR2 that could be used to guide the development of novel drugs. The current project seeks to validate the new drug target, before resource intensive efforts are made to find suitable drugs.
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.
From Lead Compounds To Potential Therapeutics: Drugs To Treat Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$523,460.00
Summary
Clostridium difficile infection (CDI) attacks the gut resulting in diarrhoea and inflammation of the colon. It is classified as the number one antibiotic-resistant bacterial threat in the USA where there are 500,000 cases of CDI and 30,000 deaths. CDI is an increasing problem for hospitalized patients in the US, the EU and Australia. Our recent NHMRC funded project established drug leads against CDI and we now require continued studies to develop our drug leads towards marketable therapeutics.
The Control And Regulatory Mechanisms Of Artemisinin Induced Dormancy In P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$495,552.00
Summary
Malaria is a major global health problem and can only be reliably treated with artemisinin combinations in many areas due to widespread of drug resistance. However a proportion of parasites appear to be able to avoid the lethal effects of the drug by becoming “dormant” following exposure. They resume growth after the drug is wanned, a feature which is reminisent to cell cycle arrest. This study investigates the role of cell cycle machinery in dormancy following arteminsinin treatment.
The Development Of Novel Antibacterials Targeting Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$750,546.00
Summary
Clostridium difficile is a bacterium associated with infections in the gut which may result in mild to severe diarrhoea and inflammation of the colon. These infections are an increasing problem for hospitalised patients in the US, the EU and Australia. We have been very successful in the past at developing new drugs to treat external infections caused by resistant strains of bacteria, for example, golden Staph. We now aim to develop our drugs to treat C. difficile infections in the gut.
Overcoming Receptor Tyrosine Kinase Mediated Resistance To BRAF Inhibitors In Metastatic Melanoma, Colorectal And Lung Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$574,958.00
Summary
The drug Vemurafenib results in good responses in melanoma patients. However, patients become resistant to treatment. We have identified specific receptors that can cause Vemurafenib resistance, which can be overcome by combination treatment with drugs to these receptors. We will assess melanoma patient samples for expression of these receptors which will be highly beneficial for selecting combination treatments to prevent drug resistance and ensure better prolonged outcomes.