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.
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 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.
Evaluation Of Novel Pyrrolo/Iminoquinone Antimalarial Compounds
Funder
National Health and Medical Research Council
Funding Amount
$614,250.00
Summary
The development of new antimalarial drugs is an unmet global health priority. In this project we will investigate novel compounds that have been found to display promising in vitro antimalarial activity. We will modify these compounds to make them more drug-like, and assess their efficacy in vivo using malaria animal models. These studies have the potential to identify compounds that may result in a new therapy for malaria, the worlds' most significant tropical infectious disease.
Development Of A Novel And Highly Selective CDK4/6 Inhibitor For Treating Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,171,199.00
Summary
We have identified and patented novel drug molecules targeting enzymes namely CDKs 4 and 6, that are important for survival of cancer cells. The drugs are highly selective and potent against CDK4/6, well absorbed orally, and have attracted much interest from a pharmaceutical company. Further detailed work is needed to characterize fully their anti-cancer effects and toxicity, thereby securing a major investment from our commercial partner for drug development for treating cancers.
Novel NLRP3 Inhibitors For Steroid Resistant Asthma
Funder
National Health and Medical Research Council
Funding Amount
$927,117.00
Summary
Asthma causes 40,000 hospitalisations p.a. with 5-10% of asthmatics having severe steroid resistant asthma, a common and debilitating disease, where current treatments do not work. Effective therapies are urgently required. Based on our research, we have novel molecules showing high level of efficacy in models of severe steroid resistant asthma. These molecules will be further investigated to deliver a drug candidate for commercialisation within 3 years.
Discovery Of New And Better Treatments For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$837,615.00
Summary
Sleeping sickness, or human African trypanosomiasis, is present in 36 countries where there are 60 million people at risk of infection, with 50,000-70,000 new cases and 48,000 deaths per annum. Transmitted by the bite of the tsetse fly, this disease is caused by the protozoan parasite Trypanosoma brucei, and without treatment, death is inevitable. We have discovered some compounds that weakly inhibit T.brucei and the aim of this project is to make them potent enough to become drug candidates.
Small Molecule Therapeutics: From Infectious And Parasitic Diseases To Cancers
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
I will lead a team of medicinal chemists to discover better treatments of diseases focused in two major domains. On one hand, I will discover new drugs to treat certain parasitic diseases such as Sleeping Sickness, Chagas disease and malaria, all caused by protozoal parasites. On the other hand, I will discover new drugs to treat certain cancers, in particular acute myeloid leukemia and Burkitt’s lymphoma, caused by dysfunction of certain types of enzymes called histone acetyltransferases.
Polymyxin-like Lipopeptide Antibiotics Of The Future
Funder
National Health and Medical Research Council
Funding Amount
$335,323.00
Summary
Polymyxins are now being clinically used as the ‘last-line’ therapy for infections caused by multidrug-resistant Gram-negative ‘superbugs’. For the first time our novel approach will interface chemistry and biology of the polymyxins with the purpose of creating a new generation of safer and more efficacious polymyxin antibiotics.