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.
Jian-kang Jiang  1 ,  Joshua G McCoy  1 ,  Min Shen  1 ,  Christopher A LeClair  1 ,  Wenwei Huang  1 ,  Ana Negri  2 ,  Jihong Li  3 ,  Robert Blue  3 ,  Amanda Weil Harrington  3 ,  Sarasija Naini  3 ,  George David 3rd  3 ,  Won-Seok Choi  3 ,  Elisabetta Volpi  3 ,  Joseph Fernandez  4 ,  Mariana Babayeva  5 ,  Mark A Nedelman  6 ,  Marta Filizola  2 ,  Barry S Coller  3 ,  Craig J Thomas  7
Affiliations
  • 1. NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, United States.
  • 2. Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
  • 3. Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY, United States.
  • 4. Proteomics Resource Center, Rockefeller University, New York, NY, United States.
  • 5. Touro College of Pharmacy, New York, NY, United States.
  • 6. Ekam Imaging, Boston, MA, United States.
  • 7. NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: [email protected].
PMID: 24461295 DOI: 10.1016/j.bmcl.2013.12.122
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.