8RZB

IL-1beta in complex with covalent DEL hit

This is a non-PDB format compatible entry.

Summary for 8RZB

• Entry DOI: 10.2210/pdb8rzb/pdb
• Related: 8RYK 8RYS
• Descriptor: Interleukin-1 beta, 8-[4-methyl-3-(trifluoromethyl)phenyl]-2-[[(7S)-7-(2-morpholin-4-ylethylcarbamoyl)-4-(phenylsulfonyl)-1,4-diazepan-1-yl]carbonyl]imidazo[1,2-a]pyridine-6-carboxylic acid (3 entities in total)
• Functional Keywords: dna-encoded library, cytokine
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 72554.38

Authors

Rondeau, J.-M.,Lehmann, S. (deposition date: 2024-02-12, release date: 2024-05-22, Last modification date: 2024-11-06)

Primary citation

Vulpetti, A.,Rondeau, J.M.,Bellance, M.H.,Blank, J.,Boesch, R.,Boettcher, A.,Bornancin, F.,Buhr, S.,Connor, L.E.,Dumelin, C.E.,Esser, O.,Hediger, M.,Hintermann, S.,Hommel, U.,Koch, E.,Lapointe, G.,Leder, L.,Lehmann, S.,Lehr, P.,Meier, P.,Muller, L.,Ostermeier, D.,Ramage, P.,Schiebel-Haddad, S.,Smith, A.B.,Stojanovic, A.,Velcicky, J.,Yamamoto, R.,Hurth, K.
Ligandability Assessment of IL-1 beta by Integrated Hit Identification Approaches.
J.Med.Chem., 67:8141-8160, 2024

PubMed Abstract: 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.

PubMed: 38728572
DOI: 10.1021/acs.jmedchem.4c00240

Experimental method

X-RAY DIFFRACTION (1.836 Å)