A-PARADDISE
Anti-Parasitic Drug Discovery in Epigenetics
| Coordinatore | INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Organization address
address: 101 Rue de Tolbiac contact info |
| Nazionalità Coordinatore | France [FR] |
| Totale costo | 8˙638˙614 € |
| EC contributo | 5˙999˙991 € |
| Programma | FP7-HEALTH
Specific Programme "Cooperation": Health |
| Code Call | FP7-HEALTH-2013-INNOVATION-1 |
| Funding Scheme | CP-FP |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-02-01 - 2017-01-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Organization address
address: 101 Rue de Tolbiac contact info |
FR (PARIS) | coordinator | 755˙604.00 |
| 2 |
KANCERA AB
Organization address
address: BANVAKTSVAGEN 22 KAROLINSKA INSTITUTET SCIENCE PARK contact info |
SE (SOLNA) | participant | 952˙100.00 |
| 3 |
FUNDACAO OSWALDO CRUZ
Organization address
address: AVENIDA BRASIL 4365 contact info |
BR (RIO DE JANEIRO) | participant | 866˙520.00 |
| 4 |
CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Organization address
address: Rue Laurent Fries 1 contact info |
FR (ILLKIRCH GRAFFENSTADEN) | participant | 440˙840.00 |
| 5 |
UNIVERSIDADE DE SAO PAULO
Organization address
address: RUA DA REITORIA 109 BUTANTA contact info |
BR (SAO PAULO SP) | participant | 411˙665.00 |
| 6 |
ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Organization address
address: FAHNENBERGPLATZ contact info |
DE (FREIBURG) | participant | 374˙400.00 |
| 7 |
UNIVERSITY OF EAST ANGLIA
Organization address
address: EARLHAM ROAD contact info |
UK (NORWICH) | participant | 334˙241.00 |
| 8 |
INSERM - TRANSFERT SA
Organization address
address: Rue Watt 7 contact info |
FR (PARIS) | participant | 313˙190.00 |
| 9 |
INSTITUT PASTEUR
Organization address
address: RUE DU DOCTEUR ROUX 25-28 contact info |
FR (PARIS CEDEX 15) | participant | 298˙598.00 |
| 10 |
UNIVERSIDADE FEDERAL DO RIO DE JANEIRO
Organization address
address: AV BRIGADEIRO TROMPOWSKI SN 2 contact info |
BR (RIO DE JANEIRO) | participant | 285˙474.00 |
| 11 |
UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Organization address
address: Piazzale Aldo Moro 5 contact info |
IT (ROMA) | participant | 284˙016.00 |
| 12 | Nome Ente NON disponibile | BR | participant | 268˙680.00 |
| 13 |
MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG
Organization address
address: UNIVERSITAETSPLATZ 10 contact info |
DE (HALLE (Saale)) | participant | 229˙800.00 |
| 14 |
ADLEGO BIOMEDICAL AB
Organization address
address: BOX 42 contact info |
SE (UPPSALA) | participant | 184˙863.00 |
| 15 |
GRIFFITH UNIVERSITY
Organization address
address: KESSELS ROAD NATHAN 170 contact info |
AU (BRISBANE) | participant | 0.00 |
| 16 |
THE UNIVERSITY OF QUEENSLAND
Organization address
address: ST LUCIA contact info |
AU (BRISBANE) | participant | 0.00 |
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Obiettivo del progetto (Objective)
'This proposal builds on the proven methodology developed in the SEtTReND FP7 project to develop inhibitors of schistosome HME as lead compounds for new drugs. We will employ a target-based strategy for the development of novel drug leads against schistosomiasis, leishmaniasis, Chagas disease and malaria by targeting histone modifying enzymes (HME), in particular those involved in acetylation/deacetylation and methylation/demethylation. The principal objectives of A-PARADDISE are: - The identification of HMEs from Leishmania sp. and Trypanosoma cruzi and the molecular characterization and functional characterization of selected potential targets, - Phenotypic screening of Leishmania, T. cruzi, S. mansoni and P. falciparum using HME class inhibitors, inhibitors developed specifically against S. mansoni and P. falciparum HMEs. This will permit us to obtain a comprehensive view of inhibitor classes and chemical scaffolds of interest, - Production of recombinant Leishmania and T. cruzi HME proteins, structural studies. Selected, validated target enzymes will be produced, crystallized and analysed by X-ray diffraction. Assays will be optimized to permit testing of inhibitors, - High-throughput and structure-based (in silico) screening of selected HMEs. Inhibitors selected will be further screened by phenotypic assays on the parasites in vitro, - Optimisation of inhibitor structures by chemical synthesis based on molecular modelling studies (inhibitors of all origins), - Transcriptomic analysis of drug-treated parasites to verify target specificity and mechanism of action (all parasites), - Pharmacological and toxicological studies (in vitro and in vivo) of selected inhibitors, in vivo testing of compounds in parasite-infected mice. The overall objective of the A-PARADDISE project is to develop optimized epigenetic inhibitors for further testing and optimisation as drug candidates against the four parasites studied.'