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NM4TB
TUBERCULOSIS
Framework programme: 6
Call: 3
Project number:
LSHP-CT-2006-018923
EC contribution: € 11,070,000
Duration: 60 months
Type: IP
Starting date: January 2006
Graphic element New Medicines for Tuberculosis
Keywords: Mycobacterium tuberculosis; multidrug resistant TB; drug development; signal transduction pathways

Summary:

New Medicines for Tuberculosis (NM4TB) aims to develop successfully new drugs for the treatment of tuberculosis (TB) through an integrated approach implemented by a team, which combines some of Europe’s leading academic TB researchers with a major pharmaceutical company and three SMEs, all with a strong commitment to discovering new anti-infective agents. NM4TB has a comprehensive portfolio of potential and validated targets plus several novel proprietary anti-TB agents in its drug development pipeline. Among the validated targets are several enzymes involved in highly druggable areas such as cell wall biogenesis, nucleic acid synthesis and central metabolic pathways for which assays amenable to high-throughput screening are available. Intensive efforts will focus on rapidly emerging targets that impact upon two, as yet, untouched areas of the physiology of M. tuberculosis signal transduction pathways and persistence.

Background:

Tuberculosis (TB) is one of the oldest diseases known to man and has infected one third of the world’s population. As a result, someone dies from the disease every 15 seconds and 30 million more people will lose their lives to TB in the next decade. Although directly observed short-course chemotherapy is available to treat the disease, this treatment is old, slow and inefficient by the current standards of the pharmaceutical industry. Here the most innovative approaches will be employed to identify and validate targets for new drugs, and implement the screening and medicinal chemistry processes required to identify lead compounds for the generation of candidate drugs.

Aims:

The aim of this project is to develop successfully new drugs for the treatment of tuberculosis (TB) with the following desired properties:

  1. high potency to reduce treatment duration
  2. activity against persistent bacilli
  3. inhibition of new target classes
  4. activity against multidrug resistant TB
  5. specificity forMycobacterium tuberculosis.

Expected results:

  1. Development and implementation of novel enabling technologies required for drug development.
  2. Target validation in well-established, ‘druggable’ areas such as the central metabolism, cell wall and nucleic acid synthesis in addition to more challenging, yet highly innovative, topics like the signal transduction and persistence mechanisms.
  3. Generation of structural information for as many targets as possible, acting iteratively in the drug development process. Structures of targets with drugs bound to rationally improve drug design.
  4. Assay development and screening of deep chemical libraries encompassing ‘active’ to ‘hit’, ‘hit’ to ‘lead’ progression, and ‘lead’ optimisation activities that give rise to candidate drugs.

Potential applications:

The proposed research will result in the development of new technologies and assays for TB drug development, discovery of new classes of lead compounds for fighting TB and lead optimisation and progression to candidate drug status.

Coordinator:

Stewart T. Cole
Unité de Génétique Moléculaire Bactérienne
Institut Pasteur,
25-28, rue du Docteur Roux,
75724 Paris Cedex 15

France
Tel: +33 1 45 68 84 46
Fax: +33 1 40 61 35 83
E-mail: stcole@pasteur.fr
Website: http://www.pasteur.fr/recherche/unites/Lgmb/

Partners:

Principal
Scientific
Participants
Official Address Other Information
2
Pedro Alzari
Unité de Biochimie Structurale
Institut Pasteur
25-28, rue du Docteur Roux
FR-75724 Paris Cedex 15
France
Tel: +33 1 45 68 86 07
Fax: +33 1 45 68 86 04
E-mail: alzari@pasteur.fr
Website: http://www.pasteur.fr/recherche/unites/Bstruct/
3
Brigitte Gicquele
Unité de Génétique Mycobactérienne
Institut Pasteur
25-28, rue du Docteur Roux
FR-75724 Paris Cedex 15
France
Tel: +33 1 45 68 88 28
Fax: +33 1 45 68 88 43
E-mail: bgicquel@pasteur.fr
Website: http://www.pasteur.fr/recherche/unites/Gemyc/
4
Alwyn T. Jones
Department of Cell and Molecular Biology
Biomedical Centre
Uppsala University
Box 596
Husargatan 3
SE-751 Uppsala
Sweden
Tel: +46 18 471 49 82
Fax: +46 18 536 971
E-mail: alwyn@xray.bmc.uu.se
Website: http://xray.bmc.uu.se/alwyn 
5
Barry Furr
AstraZeneca
Mereside
Alderley Park
UK-SK10 4TG Macclesfield
United Kingdom
Tel: +44 1625 514875
Fax: +44 1625 590115
E-mail: Barry.Furr@astrazeneca.com
Website: http://www.astrazeneca.co.uk/
6
Tanjore Balganesh
AstraZeneca R & D
Bellary Road Hebbal
Bangalore
India
Tel: +91 80 23622001 /
80 23621212
Fax: +91 80 23622002
E-mail: tanjore.balganesh@astrazeneca.com 
Website: http://www.astrazenecaindia.com/
7
Tanya Parish
Centre for Infectious Disease
Institute of Cell and Molecular Science
Barts and the London Queen Mary’s School
of Medicine and Dentistry
Turner Street
UK-E1 2AD London
United Kingdom
Tel: +44 20 7377 7000 x 2961
Fax: +44 20 7377 7259
E-mail: t.parish@qmul.ac.uk
Website: http://www.mds.qmw.ac.uk/
8
Kai Johnsson
Institute of Organic Chemistry
Laboratory of Protein Engineering
University of Lausanne
CH-1015 Lausanne
Switzerland
Tel: +41 21 693 9356 /
21 696 9350
Fax: +41 21 693 9365
E-mail: kai.johnsson@epfl.ch
Website: http://www.epfl.ch
9
Giovanna Riccardi
Dipartimento di Genetica e Microbiologia
Laboratorio di Microbiologia Molecolare
Via Ferrata, 1
IT-27100 Pavia
Italy
Tel: +39 0382 505574
Fax: +39 0382 528496
E-mail: riccardi@ipvgen.inpv.it
Website: http://unipv.it
10
Ida Rosenkrands
Statens Seruminstitut
Department of Infectious Disease Immunology
Artillerivej 5
DK-2300 Copenhagen S
Denmark
Tel: +45 32 68 37 21
Fax: +45 32 68 30 35
E-mail: idr@ssi.dk
Website: http://www.ssi.dk
11
Ute Möllmann
Hans-Knöll-Institut für Naturstoff-Forschung
Department of Infection Biology
Beutenbergstr. 11
DE-07745 Jena
Germany
Tel: +49 3641 65 6656
Fax: +49 3641 65 6652
E-mail: moellman@pmail.hki-jena.de 
Website: http://www.hki-jena.de
12
Andrew Munro
Department of Chemical Engineering and Analytical Science
University of Manchester
PO Box 88
Sackville Street
UK-M60 1QD Manchester
United Kingdom
Tel: +44 161 306 9320
Fax: +44 161 306 9321
E-mail: Andrew.Munro@manchester.ac.uk
Website: http://www.manchester.ac.uk/ 
13
Katarina Mikusova
Department of Biochemistry
Comenius University
Mlynska dolina
SK-84215 Bratislava
Slovakia
Tel: +421 2 60296 547 /
2 60296 452
Fax: +421 2 60296 452
E-mail: mikusova@fns.uniba.sk
Website: http://www.fns.uniba.sk
14
Michael Arand
Institute of Pharmacology and Toxicology
University of Zurich
Winterthurerstr. 190
Zurich
Switzerland
Tel: +41 44 6355977
Fax: +41 44 635685
E-mail: arand@pharma.unizh.ch
Website: http://www.unizh.ch
15
Kéri György
Vichem Chemie Research Ltd
Herman Ottó u. 15
Budapest
Hungary
Tel: +36 14 872 080
Fax: +36 14 872 087
E-mail: gykeri@vichem.hu
Website: http://www.vichem.hu/
16
David Rees
Medicinal Chemistry
Astex Technology
436 Cambridge Science Park
Milton Road
UK-CB3 0RU Cambridge
United Kingdom
Tel: +44 1223 226200
Fax: +44 1223 226201
E-mail: D.Rees@astex-technology.com
Website: http://www.astex-technology.com 
17
Daniela Jabes
Pharmacology
NeED Pharmaceuticals
Via Volta, 4
IT-22070 Cassina Rizzardi
Italy
Tel: +39 0348 786 9120
Fax: +39 0348 786 9121
E-mail: daniela_jabes@hotmail.com, djabes@needpharma.com
Website: http://www.needpharma.com
18
Philip Butcher
St. George’s Hospital Medical School
Cranmer Terrace
UK-SW17 ORE London
United Kingdom
Tel: +44 20 8725 5721
Fax: +44 20 8672 0234
E-mail: butcherp@sghms.ac.uk
Website: http://www.bugs.sghms.ac.uk
19
Mamadou Daffé
Institut de Pharmacologie et de Biologie Structurale
Route de Narbonne
FR-31077 Toulouse
France
Tel: +33 5 61 17 55 69
Fax: +33 5 61 17 55 80
E-mail: mamadou.daffe@ipbs.fr  
Website: http://www.ipbs.fr  

 
 
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