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Heparanase inhibitors in antiangiogenic and antimetastatic cancer therapy

Objective

Inhibition of heparanase overexpressed by tumours, preventing not only the release and activation of angiogenic growth factors stored by heparan sulfate (HS) proteoglycans but also the disruption of the basement membrane and the extracellular matrix is regarded as a very promising strategy to develop anticancer drugs. This project aims at:
a) mapping the binding sites of heparanase for HS;
b) determining the structural requirements of HS-like polysaccharides for interaction with the enzyme as substrates and as inhibitors;
c) improving the heparanase-inhibiting properties of polysaccharides by generating specific sulfation patterns optimised on biological activity (inhibition of heparanase, antimetastatic-antiangiogenic activity).

These aims will be pursued through a study of the inhibition of heparanase with natural and synthetic HS-like oligo/polysaccharides, glycomimetics, and its in vivo effects.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

ISTITUTO SCIENTIFICO DI CHIMICA E BIOCHIMICA "G.RONZONI"
Address
Via Giuseppe Colombo 81
20133 Milano
Italy

Participants (6)

BIOTIE THERAPIES OY LTD
Finland
Address
Tykistoekatu 6
20520 Turku / Abo
HADASSAH MEDICAL ORGANIZATION
Israel
Address
Kiryat Hadassah, Ein Kerem
91120 Jerusalem
Institute of Chemistry, Slovak Academy of Sciences
Slovakia
Address
Dubravska Cesta 9
84538 Bratislava
SIGMA TAU INDUSTRIE FARMACEUTICHE RIUNITE S.P.A
Italy
Address
Viale Shakerpeare 7
00144 Roma
THE UNIVERSITY OF MILANO
Italy
Address
Via Venezian 21
20133 Milano
UPPSALA UNIVERSITY
Sweden
Address
Sankt Olofsgatan 10 B
75105 Uppsala