A novel class of ion displacement ligands as antagonists of the αIIbβ3 receptor that limit conformational reorganization of the receptor

Bioorg Med Chem Lett. 2014 Feb 15;24(4):1148-53. doi: 10.1016/j.bmcl.2013.12.122. Epub 2014 Jan 8.

Abstract

A collection of αIIbβ3 integrin receptor antagonists possessing a unique MIDAS metal ion displacement mechanism of action is presented. Insight into these agents' structure-activity relationships, binding modality, and pharmacokinetic and pharmacodynamic profiles highlight the potential of these small molecule ion displacement ligands as attractive candidates for clinical development.

Keywords: Ion displacement ligand; Platelet; αIIbβ3 Integrin receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Blood Proteins / chemical synthesis
  • Blood Proteins / chemistry
  • Blood Proteins / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Ions / chemistry
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Platelet Aggregation / drug effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Blood Proteins
  • Ions
  • Ligands
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • platelet adhesion inhibitor