Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations

Abstract

The integrinα Vβ3 receptor has been implicated in several important diseases, but no α Vβ3 antagonists are approved for human therapy. One possible limitation of current small molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small molecule pure antagonists TDI-4161 and TDI-