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The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Dredge, Keith, Hammond, Edward, Davis, Kat, Li, Cai Ping, Liu, Ligong, Johnstone, Ken, Handley, Paul, Wimmer, Norbert, Gonda, Thomas, Gautam, Anand, Ferro, Vito, & Bytheway, Ian (2010) The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy. Investigational New Drugs, 28(3), pp. 276-283.

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Abstract

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Impact and interest:

22 citations in Scopus
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18 citations in Web of Science®

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ID Code: 27943
Item Type: Journal Article
Keywords: Heparan sulfate, angiogenesis, heparanase, cancer therapy
DOI: 10.1007/s10637-009-9245-5
ISSN: 1573-0646
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PHARMACOLOGY AND PHARMACEUTICAL SCIENCES (111500) > Pharmacology and Pharmaceutical Sciences not elsewhere classified (111599)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Past > Schools > School of Physical & Chemical Sciences
Copyright Owner: Copyright 2010 Springer Netherlands
Copyright Statement: The original publication is available at www.springerlink.com
Deposited On: 14 Oct 2009 14:08
Last Modified: 30 Oct 2013 13:09

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