Ligands to the integrin receptor α_vβ₃

Abstract

The vitronectin receptor _vβ₃ is a member of the integrin superfamily of membrane bound glycoprotein receptors that is responsible for cell-cell and cell-matrix interactions and shares the same β subunit as the fibrinogen receptor _IIbβ₃ (also known as GPIIb/IIIa). Both these integrins recognise extracellular proteins that express the peptide sequence arginine-glycine-aspartic acid (RGD). Non-peptide RGD mimetics that bind with high affinity and selectivity to _IIbβ₃ were previously prepared as anti-thrombotic agents. More recently, medicinal chemistry groups have modified these non-peptide fibrinogen receptor antagonist lead structures to impart potency and integrin selectivity for _vβ₃. Numerous patent applications and issued patents have appeared throughout the last decade claiming structurally novel _vβ₃ antagonists as agents for the prevention and/or treatment of osteoporosis, cancer, diabetic retinopathy and rheumatoid arthritis. This review encompasses those issued patents and published patent applications that disclose ligands to _vβ₃.

• αvβ3
• angiogenesis
• integrin
• osteoporosis
• vitronectin