A Novel Small-Molecule Integrin Antagonist Inhibits Cells Adhesion Followed By Anoikis in Endothelial Cells - A Comparative Analysis with Cilengitide

Background: Despite the crucial role of integrin receptors in cancer pathogenesis and massive efforts towards establishing clinically relevant drugs, to the present no effective integrin antagonist for the treatment of malignant diseases has been introduced into the clinic. Context and purpose of the study: The purpose of the study was to examine the cellular effects and molecular mechanisms of a novel anti-integrin compound designated AV-398/38 and to compare it with cilengitide, one of the most advanced and best characterized αVβ3/αVβ5 integrin antagonists. AV-398/38 is a small molecule integrin antagonist that is currently in an early phase of pre-clinical evaluation. It was identified by virtual screening of chemical databases with the aim to detect novel integrin αVβ3 antagonist-like candidates. Based on preliminary in vitro data, the compound was recognized as a potential anti-neoplastic drug candidate, displaying high specificity and binding affinity in the nanomolar range towards the αVβ3 receptor, as well as showing potentially favorable drug-like properties.