Peroxovanadium compounds as protein tyrosine phosphatase (ptp) inhibitors: theirinhibitory effects on angiogenesis, restenosis and the production of endothelin s, and their stimulating effects on the immune response

摘要

The present invention relates to the use of peroxovanadium compounds in the prevention of angiogenesis, restenosis and the production of endothelins, and as immunomodulators. Peroxovanadium compounds are preferred since they are more potent, and less toxic, than their "oxo" counterparts. Anti-angiogenic activity was verified in vitro against human umbilical vascular endothelial cells (HUVECs) as well as ex ovo using the chicken chorioallantoic assay membrane and in the rat aortic ring model and a Matrigel assay in vivo. Peroxovanadium compounds also decrease basal levels and inhibit the increase in plasma endothelins occurring following insulin induction in rats. It is proposed that peroxovanadium compounds are therapeutically-active anti-angiogenics and useful in preventing vascular restenosis by acting, inter alia, by inhibiting one or several protein tyrosine phosphatases (PTPs) involved in the proliferation, differentiation and migration of cells or the secretion of peptides (such as endothelins and immunomodulators), or both.