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

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.

journal_name

Invest New Drugs

authors

Dredge K,Hammond E,Davis K,Li CP,Liu L,Johnstone K,Handley P,Wimmer N,Gonda TJ,Gautam A,Ferro V,Bytheway I

doi

10.1007/s10637-009-9245-5

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

276-83

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

28

pub_type

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