NOXYCANCERSTARV

Synthesis of N-hydroxyheterocycles as starvation agents against highly invasive hypoxic solid tumours

Coordinatore	UNIVERSITA DI PISA    more  Organization address address: Lungarno Pacinotti 43/44 city: PISA postcode: 56126 contact info Titolo: Dr. Nome: Francesca Cognome: Lombardi Email: send email Telefono: +39 050 2219545 Fax: +39 050 2219577
Nazionalità Coordinatore	Italy [IT]
Totale costo	0 €
EC contributo	173˙825 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-IIF-2008
Funding Scheme	MC-IIF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-07-01   -   2011-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITA DI PISA  Organization address address: Lungarno Pacinotti 43/44 city: PISA postcode: 56126 contact info Titolo: Dr. Nome: Francesca Cognome: Lombardi Email: send email Telefono: +39 050 2219545 Fax: +39 050 2219577	IT (PISA)	coordinator	173˙825.86

Mappa

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 Obiettivo del progetto (Objective)

'The purpose of this research project is the development of preclinical anti-cancer drug candidates able to fight hypoxic solid tumours, which are normally resistant to chemotherapy and radiotherapy. Highly invasive tumour cells are characterized by a metabolic switch, known as the Warburg effect, from “normal” oxidative phosphorylation to an increased anaerobic glycolysis. This ensures a sufficient energy supply from glucose, even in hypoxic environments. One of the key enzymes involved in anaerobic glycolisis, the muscle isoform of lactate dehydrogenase (LDH5), has been recently shown to be overexpressed by metastatic cancer cells, and has been linked to the vitality of tumours in hypoxia. This enzyme may be considered as a valid target for new anticancer agents, since its inhibition would lead to a cut in cancer energy supply, thus reducing its metastatic and invasive potential. A validation of LDH5 as a safe target derives from the observation that in humans, hereditary LDH5 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. Each step of his formation will be adequately followed by additional specialized trainers. The host institution has already identified a suitable structural scaffold, based on N-hydroxyheterocycles, which has furnished some preliminary LDH5 inhibitors, comparable to those observed with the few examples known in literature. This scaffold constitutes the basis for the development of a large series of analogues, and thus it increases the chances of finding highly active new LDH5 inhibitors, which will constitute pre-clinical candidates for the treatment of metastatic cancer.'

Introduzione (Teaser)

Invasive and highly resistant to treatment, metastatic cancer is one of the leading causes of death. Inhibiting key enzymes found predominantly in cancer cells can safely and effectively reduce the growth and spread of cancer.