European Gram Negative Antibacterial Engine

Lead Research Organisation: John Innes Centre
Department Name: Contracts Office

Abstract

The intensive use and misuse of antibiotics has resulted in antibiotic resistance in essentially all human bacterial pathogens. This is especially true when considering resistant Gram-negative infections where resistance is rising and use of drugs of last resort, such as colistin, is increasing. The New Drugs 4 Bad Bugs (ND4BB) initiative is a series of programmes designed to directly address some of the scientific challenges associated with antibacterial drug discovery and development. The ND4BB ENABLE consortium will meet these challenges by creating and optimising a portfolio of new antibiotics ranging from Hits through Phase 1 clinical studies.
The goals of the ENABLE consortium are to:
1. create a drug discovery platform with the expertise and resource base to prosecute multiple antibacterial programmes in parallel;
2. increase the overall pipeline in the antibacterial area by applying this platform to optimise a variety of antibacterial programmes.
More specifically the key objectives of the consortium are designed to increase the overall pipeline of high quality, novel mode of action medicines to treat serious systemic Gram-negative infections by identifying three antibacterial Leads, two antibacterial Candidates and progressing at least one compound into preclinical and Phase 1 clinical studies. The platform group is made up of academics and SMEs from across Europe with diverse expertise and includes 4 large pharma companies. The consortium will provide a unique opportunity for a productive collaboration between academic researchers and industry.
The role of the JIC group in this consortium is to evaluate compounds from other consortium partners as inhibitors of topoisomerases (DNA gyrase and topo IV) from various Gram-negative bacterial species. Positive compounds will be investigated further in terms of their mechanisms of inhibition and structures of the ligand-target complexes using X-ray crystallography.

Publications

10 25 50
 
Description We have collaborated on the development of two new groups of antibiotics targeted to Gram-negative pathogenic bacteria; three papers published so far.
Exploitation Route The companies involved in the consortium are in a position to develop the compounds into clinically useable antibiotics
Sectors Pharmaceuticals and Medical Biotechnology

URL http://nd4bb-enable.eu/
 
Description Consortium compounds are using new findings for drug discovery
First Year Of Impact 2016
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Bax 
Organisation Cardiff University
Department Cardiff Synthetic Biology Initiative
Country United Kingdom 
Sector Academic/University 
PI Contribution We have performed mechanistic enzymology work to complement the structural biology performed by Bax and others.
Collaborator Contribution They have established a crystallography platform to analyse structures of topoisomerase-DNA-drug complexes. That expertise has now been transferred to JIC.
Impact Research publications. Multi-disciplinary: biochemistry, crystallography, molecular biology
Start Year 2014
 
Description Fishwick 
Organisation University of Leeds
Department University of Leeds Special Collections
Country United Kingdom 
Sector Academic/University 
PI Contribution We have been testing compounds synthesised by the med chem research team in Leeds
Collaborator Contribution Using information provided by us, they have been using computational and medicinal chemistry methods to synthesise novel compounds that have antibacterial potential
Impact Grant application to the Wellcome Trust currently under consideration
Start Year 2017
 
Description IMI consortium: ENABLE 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We carried out the biochemical/molecular biological aspects of the projects
Collaborator Contribution Drug discovery and medicinal chemistry and x-ray crystallography
Impact Publications
Start Year 2014