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

被引：92

作者：

Dredge, K. ^{[1
]}

Hammond, E. ^{[1
]}

Davis, K. ^{[1
]}

Li, C. P. ^{[1
]}

Liu, L. ^{[1
]}

Johnstone, K. ^{[1
]}

Handley, P. ^{[1
]}

Wimmer, N. ^{[1
]}

Gonda, T. J. ^{[2
]}

Gautam, A. ^{[1
]}

Ferro, V. ^{[1
]}

Bytheway, I. ^{[1
]}

机构：

[1] Progen Pharmaceut Ltd, Drug Design Grp, Brisbane, Qld 4066, Australia

[2] Univ Queensland, Diamantina Inst, Mol Oncogenesis Grp, Brisbane, Qld, Australia

来源：

INVESTIGATIONAL NEW DRUGS | 2010年 / 28卷 / 03期

关键词：

Heparan sulfate; Angiogenesis; Heparanase; Cancer therapy; PROGRESSION; GROWTH; METASTASIS; PI-88;

D O I：

10.1007/s10637-009-9245-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：276 / 283

页数：8

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