1. Selectins in Biology and Human Disease: Opportunity in E-selectin Antagonism.
- Author
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Peterson JM, Smith TA, Rock EP, and Magnani JL
- Abstract
Selectins are cell adhesion proteins discovered in the 1980s. As C-type lectins, selectins contain an essential calcium ion in the ligand-binding pocket and recognize the isomeric tetrasaccharides sialyl Lewis
x (sLex ) and sialyl Lewisa (sLea ). Three selectins, E-selectin, P-selectin, and L-selectin, play distinct, complementary roles in inflammation, hematopoiesis, and tumor biology. They have been implicated in the pathology of diverse inflammatory disorders, and several selectin antagonists have been tested clinically. E-selectin plays a unique role in leukocyte activation, making it an attractive target for intervention, for example, in sickle cell disease (SCD). This review summarizes selectin biology and pathology, structure and ligand binding, and selectin antagonists that have reached clinical testing with an emphasis on E-selectin., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: John M. Peterson declare(s) employment, a patent, stock/stock options and travel from GlycoMimetics, Inc. Edwin P. Rock declare(s) employment, stock/stock options and travel from GlycoMimetics, Inc. John L. Magnani declare(s) personal fees, employment and stock/stock options from GlycoMimetics, Inc. Theodore A. Smith declare(s) employment, a patent and stock/stock options from GlycoMimetics, Inc. Intellectual property info: All authors are currently or were recently employees of GlycoMimetics Inc. As such, we have been involved in the discovery and development of the E-selectin antagonists uproleselan and GMI-1687, as well as the pan-selectin antagonist rivipansel, which are described in this manuscript. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Peterson et al.)- Published
- 2024
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