Discovery of novel IL-17 inhibitors by scaffold morphing strategy
The proinflammatory cytokine interleukin IL-17 (IL-17) plays an important role in the immune response to fungal and bacterial infections.1 An overexpression of IL-17 is associated with various autoimmune and inflammatory diseases including psoriasis, psoriatic arthritis and ankylosing spondylitis.2 The role of IL-17 in these diseases was validated by the clinical use of IL-17 neutralizing monoclonal antibodies like secukinumab (Cosentyx).3 Recently, many organizations conducted research aimed at discovery of low molecular weight IL-17 inhibitors.4 In this talk, our work towards identification of structurally diverse small molecule IL-17 inhibitors will be presented. The focus will be on the scaffold morphing activities aiming to mask or replace the amides in the known IL-17 scaffold.
[1] Kingston H. G. Mills, Nature Reviews Immunology 2023, 23, 38– 54.
[2] Longjie Huangfu, Ruiying Li, Yamei Huang, Shan Wan, Signal Transduction and Targeted Therapy 2023, 8, 402.
[3] Frank Kolbinger, Franco Di Padova, Atul Deodhar, Jason E. Hawkes, Christine Huppertz, Torsten Kuiper, Iain B. McInnes, Christopher T. Ritchlin, David Rosmarin, Georg Schett, José M. Carballido, Peter Häusermann, Claudio Calonder, Beate Vogel, Jean-Michel Rondeau, Gerard Bruin, Pharmacology & Therapeutics 2022, 229, 107925.
[4] Bidong Zhang, Alexander Dömling, Expert Opinion on Therapeutic Patents 2022, 32, 1161– 1173.