Oxford Drug Design (formerly InhibOx) has started work on a $1.1m (£900k) grant funded project to develop novel antibiotics. The project started four years ago as part of an EU-funded collaboration into multi-drug resistance. Capitalising on drug design, chemical synthesis and biology skills across the consortium, they have discovered new molecules with activity against a range of Gram-negative bacteria. The new money comes from Innovate UK, the UK’s innovation agency, as part of the biomedical catalyst fund and will be used to design dual target inhibitors of aminoacyl tRNA synthetases for the treatment of multi-drug-resistant infections.
The compounds discovered so far inhibit a member of the tRNA synthetase family which plays a key role in protein biosynthesis. They have activity against a range of Gram-negative bacteria but need to be improved in terms of the level of activity and stability. This class of bacteria (which includes species such as E. coli and Klebsiella) has an extra layer to their cell wall. This provides them with an additional barrier to drug penetration, making them much harder to treat. By targeting more than one tRNA synthetase improvements should be seen in terms of both activity and decreased levels of bacterial resistance.
The next steps are to optimize the molecules to enhance their activity and stability and to monitor the emergence of resistance. The design work will be carried by over the next two years with the aim of developing a candidate ready for clinical testing.