Compound class:
Synthetic organic
Comment: This is the most potent compound developed via a pharmacophore and docking-based virtual screening campaign aimed at the discovery of small molecule inhibitors of the IL-15/IL-15R interaction [2]. Specifically, the investigators were searching for compounds that inhibit IL-15 binding to the IL-2Rβ subunit which together with the γ subunit, forms the signal transducing component of the IL-15R complex. Although the compound was found to be non-selective for IL-15 over IL-2, as a first in vitro SAR study it provides crucial information on the key binding interactions of IL-15 with its IL-2Rβ binding site, that will be useful for futher compound optimisation.
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References |
1. Mortier E, Quéméner A, Vusio P, Lorenzen I, Boublik Y, Grötzinger J, Plet A, Jacques Y. (2006)
Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and potent agonist of IL-15 action through IL-15R beta/gamma. Hyperagonist IL-15 x IL-15R alpha fusion proteins. J Biol Chem, 281 (3): 1612-9. [PMID:16284400] |
2. Quéméner A, Maillasson M, Arzel L, Sicard B, Vomiandry R, Mortier E, Dubreuil D, Jacques Y, Lebreton J, Mathé-Allainmat M. (2017)
Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization. J Med Chem, 60 (14): 6249-6272. [PMID:28657314] |