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

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

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.

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