Antimicrobial-resistant infections currently claim at least 50,000 lives each year across Europe with worldwide annual casualties estimated to reach 10 million by 2050.*
Oxford Drug Design has identified a new class of antibiotics that have shown promise against a range of key Gram-negative organisms. We are currently improving the activity and other properties of these compounds whilst minimizing the chances of resistance arising.
Working with our partners in the NABARSI consortium, Oxford Drug Design has discovered inhibitors of aaRS enzymes. Using our drug-design expertise, we have optimized these compounds to introduce antibacterial activity and developed a backup class of compounds. Our cheminformatics analysis of antibacterial molecules has helped guide us to the right area of chemical space to exhibit antibacterial activity. We continue to apply machine-learning techniques to gain a better understanding of antibacterial properties.
The two compound series have antibiotic activity against Gram-negative pathogens including several key ESKAPE organisms and resistant strains that are urgent and serious threats to public health. The compounds are not cross-resistant to existing classes of antibiotics, such as penicillins and fluoroquinolones and we are pursuing novel strategies to minimize the development of resistance, in order to improve clinical utility.
We are currently improving potency and spectrum of activity as we advance the compounds towards clinical candidate status.
This work is partly funded by Innovate UK, the UK's innovation agency, and previously by the European Union Framework Programme 7.
ODD is developing novel classes of compounds as inhibitors of bacterial histidine kinases, part of the bacterial quorum sensing pathway. These have the opportunity to effect bacterial virulaence without introducing selection pressures that can lead to resistance.
This work is partly funded by the European Union’s Horizon 2020 Marie Curie European Training Network - CARTNET, “Combating Antimicrobial Resistance Training Network”, under grant agreement No 765147.
Further pre-clinical antibacterial projects focused on novel mechanisms of action and with potential human and veterinary applications complete the Oxford Drug Design pipeline of drug discovery projects. Applications to parasitic diseases and other therapeutic areas are also envisaged.