Patent Evaluation: Desulphated Heparin Analogues as Antimetastatic Agents

Summary

Novelty: Glycosaminoglycan derivatives, potentially useful for impeding tumour metastasis or tumour invasiveness, are disclosed. The glycosaminoglycan, heparin, is a preferred compound for derivitization. Such derivatives retain heparinase inhibitory activity but are substantially devoid of anticoagulant properties.

Biology: An in vivo rodent study evaluating inhibition of metastatic melanoma colonization by heparin derivatives, is described. Male C57BL/6 mice were inoculated iv with 50,000 B16-BL melanoma cells. Treated mice were intravenously injected with 0.1 ml (5.0 mg/ml) of test compound, four hours before and twenty hours after inocluation. Carboxyl reduced heparin shows the greatest inhibitory activity, six lung colonies (median) having been formed. This compares with the formation of <150 colonies (median) in untreated animals.

Chemistry: Derivitization is carried out via standard techniques. Details are presented.