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LEISHDRUG

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Cerrado

Targeting the Leishmania kinome for the development of novel anti parasitic stra...

Targeting the Leishmania kinome for the development of novel anti parasitic strategies Visceral leishmaniasis is caused by the protozoan parasites Leishmania donovani and Leishmania infantum and is a potentially fatal disease in endemic areas around the world. During the infectious cycle, Leishmania alternate betwee... ver más

31/03/2012

4M€

Presupuesto del proyecto: 4M€

Líder del proyecto

INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 13 Participantes

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-03-31 No tenemos la información de la convocatoria

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13 Participantes

0.00€ | Lider

FUNDACIO PRIVADA CENTRE DE R...

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TECHNION ISRAEL INSTITUTE O...

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Líder del proyecto

INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 4M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Visceral leishmaniasis is caused by the protozoan parasites Leishmania donovani and Leishmania infantum and is a potentially fatal disease in endemic areas around the world. During the infectious cycle, Leishmania alternate between the insect promastigote stage and the vertebrate aflagellate amastigote stage that proliferates inside infected host macrophages provoking the pathology of the disease. This consortium uses a highly interdisciplinary approach to reveal Leishmania signaling molecules associated with amastigote virulence, with the major aim to exploit parasite-specific pathways for anti-leishmanial drug development. We use innovative drug screening concepts not applied previously on parasitic systems. We will utilize visual high-content screening to discover compounds capable to kill intracellular Leishmania amastigotes without deteriorating the host cell. This phenotype-based strategy relies on fluorescent parasites and macrophages as read-outs and will allow simultaneous assessment of anti-leishmanial activity and host cell toxicity under physiological conditions. We will apply a target-based strategy utilizing recombinant Leishmania protein kinases for inhibitor identification and structure-guided drug design. The identification of appropriate target kinases, with only limited homology to their mammalian counterparts will rely on in silico analysis by applying novel bioinformatic tools developed by consortium members, and in vitro assay based on their phospho-transferase activity towards recombinant Leishmania phospho-proteins. The major objectives of this proposal are (i) to screen small molecule and peptide libraries for hit compounds with leishmanicidal activity using phenotype- and target-based strategies, (ii) to identify anti-parasitic lead compounds and assess their pharmacokinetic profiles using cell-culture and experimental infection models for leishmaniasis, and (iii) to initiate lead optimization by structure-based drug design.

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