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Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches.

Vulpetti, Anna, Rondeau, Jean-Michel, BELLANCE, Marie-Helene, Blank, Jutta, Boesch, Ralf, Boettcher, Andreas, Bornancin, Frederic, Buhr, Sylvia, Connor, Lauren, Dumelin, Christoph, Esser, Oliver, Hediger, Michael, Hintermann, Samuel, Hommel, Ulrich, Koch, Elke, Lapointe, Guillaume, Leder, Lukas, Lehmann, Sylvie, Lehr, Philipp, Meier, Peter, Muller, Lionel, Ostermeier, Daniela, Ramage, Paul, Schiebel-Haddad, Sihame, Smith, Alexander Baxter, Stojanovic, Aleksandar, Velcicky, Juraj and Hurth, Konstanze (2024) Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches. Journal of medicinal chemistry, 67 (10). pp. 8141-8160. ISSN 1520-4804


Human interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1β binders that interfere with IL-1β signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening. The utilization of distinct technologies resulted in the identification of new chemical entities exploiting three different sites on IL-1β, all of them also inhibiting the interaction with the IL-1R1 receptor. Moreover, we identified lysine 103 of IL-1β as a target residue suitable for the development of covalent, low-molecular-weight IL-1β antagonists.

Item Type: Article
Keywords: Drug Discovery Interleukin-1beta Ligands, fragment-based screening, DNA-encoded library, peptide discovery platform, virtual screening
Date Deposited: 25 Jun 2024 00:46
Last Modified: 25 Jun 2024 00:46