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

Invest New Drugs. 2010 Jun;28(3):276-83. doi: 10.1007/s10637-009-9245-5. Epub 2009 Apr 9.


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.

MeSH terms

  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Discovery / methods
  • Drug Evaluation, Preclinical / methods
  • Fibroblast Growth Factor 1 / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Glucuronidase / antagonists & inhibitors*
  • Heparitin Sulfate / analogs & derivatives*
  • Heparitin Sulfate / pharmacology
  • Heparitin Sulfate / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / metabolism


  • Anticoagulants
  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Heparitin Sulfate
  • heparanase
  • Glucuronidase