LACTABLOCK

Design and synthesis of selective inhibitors of human lactate dehydrogenase 5 targeting the peculiar metabolism of glucose in tumours

Coordinatore	UNIVERSITA DI PISA    more  Organization address address: Lungarno Pacinotti 43/44 city: PISA postcode: 56126 contact info Titolo: Prof. Nome: Filippo Cognome: Minutolo Email: send email Telefono: +39 050 2219557 Fax: +39 050 2219605
Nazionalità Coordinatore	Italy [IT]
Totale costo	193˙726 €
EC contributo	193˙726 €
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-2011-IIF
Funding Scheme	MC-IIF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-07-01   -   2014-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITA DI PISA  Organization address address: Lungarno Pacinotti 43/44 city: PISA postcode: 56126 contact info Titolo: Prof. Nome: Filippo Cognome: Minutolo Email: send email Telefono: +39 050 2219557 Fax: +39 050 2219605	IT (PISA)	coordinator	193˙726.80

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'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.'