More Medicines for Tuberculosis

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

Abstract

The More Medicines for Tuberculosis (MM4TB - EU FP7) consortium has evolved from the highly successful FP6 project, New Medicines for TB (NM4TB), which delivered a candidate drug for clinical development. Building on these foundations, MM4TB will continue to develop new drugs for TB treatment. An integrated approach will be implemented by a multidisciplinary team that combines some of Europe's leading academic TB researchers with two major pharmaceutical companies and four SMEs, all strongly committed to the discovery of anti-infective agents. MM4TB will use a tripartite screening strategy to discover new hits in libraries of natural products and synthetic compounds, while concentrating on both classical and innovative targets that have been pharmacologically validated. Whole cell screens will be conducted against Mycobacterium tuberculosis using in vitro and ex vivo models for active growth, latency and intracellular infection. Hits that are positive in two or more of these models will then be used for target identification. Targets thus selected will enter assay development, structure determination, fragment-based and rational drug design programs; functionally related targets will be found using metabolic pathway reconstruction. The role of JIC (AM lab) will be to develop M. tuberculosis gyrase as a target and establishing the mechanism of action of novel compounds that target this enzyme. This will involve biochemistry and structural methods (X-ray crystallography), carried out in collaboration with the Lawson laboratory. Medicinal chemistry, carried out in other labs in the consortium, will convert leads to molecules with drug-like properties for evaluation of efficacy in different animal models and late preclinical testing.

Publications

10 25 50
 
Description We have evaluated about 300,000 compounds for their potential as anti-TB compounds. Some of these will be considered as new TB drugs.
Exploitation Route Others may pick up these findings and use the data in drug-development programmes
Sectors Pharmaceuticals and Medical Biotechnology

URL http://www.mm4tb.org/
 
Description The EU team have been exploring novel compounds as potential TB agents. Some of these compounds will be used to develop new TB drugs.
First Year Of Impact 2014
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Nagaraja 
Organisation Indian Institute of Science
Country India 
Sector Academic/University 
PI Contribution Collaborative experiments and provision of materials. Detailed discussions on projects
Collaborator Contribution Collaborative experiments and provision of materials. Detailed discussions on projects
Impact Several research papers
 
Description mm4tb 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution We were one of ~25 labs on the EU-funded More Medicines for Tuberculosis consortium. Our role was to provide expertise etc on M. tuberculosis gyrase to evaluate compounds provided by other consortium members.
Collaborator Contribution Principally to provide new compounds for evaluation
Impact Several publications (some still in the pipeline); several bilateral collaborations
Start Year 2011
 
Description London International Youth Forum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact • Aug 2017 - lecture to students visiting as part of London International Youth Science Form: 'Where will the new antibiotics come from?'
Year(s) Of Engagement Activity 2017