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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Immunopharmacology Comments |
IL-15 plays important roles in innate and adaptative immunity (promoting the activation and proliferation of NK, NK-T, and CD8+ T cells for example), and high expression levels are associated with inflammatory and autoimmune diseases. The development of small molecules with the potential to disrupt IL-15 receptor signalling is one of various antagonistic approaches being investigated for clinical utility. In this case researchers are attempting tp develop small molecules that inhibit protein-protein interactions at the interface of IL-15 and its receptor, specifically in this case with the IL-2Rβ component of the IL-15R complex. |