When: Wednesday, June 15th, 2022, 14 p.m.

Where: Faculty of Science, Amphi G, Bld 28.

Title: Design, Synthesis and Evaluation of Small Molecule Inhibitors of the Interleukin (IL)-15 System. 

Abstract: Interleukin (IL)-15, is a pleiotropic cytokine structurally close to IL-2, both sharing the IL-2Rβ and γc receptor subunits. IL-15 plays important roles in innate and adaptative immunity, supporting the activation and proliferation of NK, NK-T, and CD8+ T cells. In case of dysregulation, high levels of IL-15 have been detected, leading to abnormal immune responses and autoimmune or inflammatory diseases such as polyarthritis rheumatoid or psoriasis. Hence, our goal is to synthesize small molecule inhibitors that bind specifically to IL15 on the IL-2Rβ interface. Herein, we describe two new families of IL-15 inhibitors.  Taking advantage of our previous work, extending modifications were done on our first series called IBI. On a second time, we applied a similar docking-based virtual screening of compounds libraries on a refined pharmacophore-based on IL-15 specific residues identified on the binding site of IL-15 with IL- 2Rβ giving so our second family named IBIS. These series of compounds were evaluated for their capacity to inhibit the binding to IL-15 to its cognate receptor, as well as the down-stream signaling of IL-15-dependent cells and their proliferation