1026073-56-2Relevant articles and documents
Nanomolar e-selectin antagonists with prolonged half-lives by a fragment-based approach
Egger, Jonas,Weckerle, Celine,Cutting, Brian,Schwardt, Oliver,Rabbani, Said,Lemme, Katrin,Ernst, Beat
supporting information, p. 9820 - 9828 (2013/07/26)
Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewisx (sLex), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLex mimic were identified. A library of antagonists obtained by connecting the sLex mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with KD values ranging from 30 to 89 nM. In contrast to carbohydrate-lectin complexes with typical half-lives (t1/2) in the range of one second or even less, these fragment-based selectin antagonists show t1/2 of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.
HETEROBIFUNCTIONAL INHIBITORS OF E-SELECTINS AND CXCR4 CHEMOKINE RECEPTORS
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Page/Page column 12; 33, (2010/11/17)
Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.