Angiogenesis inhibitors antitumor agents: pharmacophore models to ;anb;3 antagonists

Abstract

Cancer is one of the leading causes of death. Angiogenesis, the growth of new blood vessels, is essential for tumor development and spreading. Integrins are a family of surface receptors that are involved in angiogenesis. The ;anb;3 integrin plays an important role in tumor angiogenesis. ;anb;3 inhibitors have direct effects to prevent tumor metastases, growth and angiogenesis. In vitro screening of cyclic peptide libraries led to highly active and ;anb;3-selective compounds. Non-peptidic ;anb;3 antagonists were also designed and synthesized. The crystal structure of the ;anb;3 integrin in complex with RGD ligant allowed structure-based rational design of ligands and validation of pharmacophore model to ;anb;3 antagonists.