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

Paradigms and Technologies

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.

Authors

Jiang, Jian-Kang; McCoy, Joshua G; Shen, Min; LeClair, Chris; Huang, Wenwei; Negri, Ana; Li, Jihong; Blue, Robert; Harrington, Amanda Weil; Naini, Sarasija; David, George; Choi, Won-Seok; Volpi, Elisabetta; Fernandez, Joseph; Babayeva, Mariana; Nedelman, Mark A; Filizola, Marta; Coller, Barry S; Thomas, Craig;

Keywords

  • 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

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