Novel safer polymyxins
Polymyxins are increasingly used as the last-line therapy against Gram-negative superbugs, which are resistant to all other currently available antibiotics. Unfortunately, nephrotoxicity is a major dose-limiting factor, and resistance to polymyxins is emerging. There is an urgent unmet medical need to discover new antibiotics with superior activity against these problematic human pathogens.
Funded by the US National Institutes of Health, D4's antimicrobial discovery program employs novel structure-activity relationship and structure-nephrotoxicity relationship models, and is strongly supported by our 15-year polymyxin pharmacological research. D4 researchers have established an efficient total synthesis platform to produce novel polymyxins for pharmacological evaluations. A number of lead compounds have been identified and are currently undergoing comprehensive toxicity evaluations.
Cell wall synthesis inhibitors
Beta-lactam antibiotics are one of the most successful drug classes of all times. They represent the largest and most commonly used antibiotic class and are very safe in patients of all ages. All beta-lactam antibiotics target penicillin-binding proteins. These enzymes catalyse critical steps in the synthesis and remodelling of the bacterial cell wall.
D4 researchers are seeking to develop innovative cell wall synthesis inhibitors that are substantially less affected by bacterial resistance mechanisms, and provide valuable additions to our therapeutic armamentarium against multi-drug-resistant bacterial superbugs.
Antivirals against Hendra and Ebola viruses
Emerging viruses, such as Hendra and Ebola, are a global threat to human health. The antiviral discovery team of D4's anti-infective program specifically investigates:
- the structure and receptor binding properties of influenza virus haemagglutinin
- developing small-molecule therapeutics against the Hendra and Ebola viruses
This research program is funded by the National Health and Medical Research Council and CSL.