Frank Narjes, Fredrik Edfeldt, Jens Petersen, Linda Öster, Corinne Hamblet, James Bird, Peter Bold, Rebecca Rae, Elisabeth Bäck, Stina Stomilovic, Pavol Zlatoidsky, Tor Svensson, Lotta Hidestål, Lavaniya Kunalingam, Igor Shamovsky, Leonardo De Maria, Euan Gordon, Richard J Lewis, Sophie Watcham, Katerine van Rietschoten, Gemma E Mudd, Helen Harrison, Liuhong Chen, Michael J Skynner
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that is difficult to drug with conventional small molecules due to the extended protein-protein interactions it forms with both receptors. The hit series was shown to bind to TSLP in a hotspot, that is also used by IL-7Rα...
January 29, 2024: Journal of Medicinal Chemistry