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LACTABLOCK

Financiado

Cerrado

Design and synthesis of selective inhibitors of human lactate dehydrogenase 5 ta...

Design and synthesis of selective inhibitors of human lactate dehydrogenase 5 targeting the peculiar metabolism of glucose in tumours "Highly invasive tumour phenotypes show a metabolic switch (Warburg effect) from oxidative phosphorylation to an increased glycolysis. This change in glucose metabolism, in favour of a less efficient process for production of ener... ver más

30/06/2014

UNIPI

194K€

Presupuesto del proyecto: 194K€

Líder del proyecto

UNIVERSITA DI PISA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2014-06-30 No tenemos la información de la convocatoria

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UNIPI

0.00€ | Lider

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Líder del proyecto

UNIVERSITA DI PISA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 194K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "Highly invasive tumour phenotypes show a metabolic switch (Warburg effect) from oxidative phosphorylation to an increased glycolysis. This change in glucose metabolism, in favour of a less efficient process for production of energy and anabolites, confers several advantages on the tumour cells, such as the ability to grow in poorly oxygenated conditions, which are typical of invasive hypoxic tumours. One of the key enzymes actively involved in anaerobic glycolysis, the muscle isoform of human lactate dehydrogenase (hLDH5), was shown to be overexpressed by metastatic cancer cells, and has been linked to the vitality of tumours in hypoxia. This enzyme is currently being considered as a valid target for new anticancer agents, since its inhibition leads to a cut in cancer energy supply, thus reducing its metastatic and invasive potential. A validation of hLDH5 as a safe target derives from the observation that in humans, hereditary hLDH5 deficiency causes a certain level of myopathy only after intense anaerobic exercise, whereas it does not provoke any symptoms under ordinary circumstances. This project will support a qualified international researcher in the management of a research line including molecular design and synthesis of a series of new compounds, as well as in the participation in the biological evaluation of their properties. The host institution has already discovered a suitable structural scaffold, based on N-hydroxyheterocycles (NHIs), which has furnished some efficient hLDH5-inhibitors, possessing first-in-class potency and isoform selectivity. This scaffold will constitute the basis for the development of larger series of optimized NHI-analogues, as well as for appropriate variations of the central NHI-scaffold, leading to completely new classes of hLDH5-inhibitors, which will constitute more suitable pre-clinical candidates for the treatment of metastatic cancer."

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