Artikel ; Online: Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.
Journal of medicinal chemistry
2024 Band 67, Heft 8, Seite(n) 6456–6494
Abstract: Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule ...
| Abstract | Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer. |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mesh-Begriff(e) | Interleukin-17/metabolism ; Interleukin-17/antagonists & inhibitors ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; DNA/metabolism ; DNA/chemistry ; Humans ; Drug Discovery ; Animals ; Structure-Activity Relationship ; Protein Binding ; Mice | ||||||||||
| Chemische Substanzen | Interleukin-17 ; Small Molecule Libraries ; DNA (9007-49-2) ; IL17A protein, human | ||||||||||
| Sprache | Englisch | ||||||||||
| Erscheinungsdatum | 2024-04-04 | ||||||||||
| Erscheinungsland | United States | ||||||||||
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 218133-2 | ||||||||||
| ISSN | 1520-4804 ; 0022-2623 | ||||||||||
| ISSN (online) | 1520-4804 | ||||||||||
| ISSN | 0022-2623 | ||||||||||
| DOI | 10.1021/acs.jmedchem.3c02397 | ||||||||||
| Signatur |
|
||||||||||
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
| Zs.B 151: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MB 1: Hefte anzeigen |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.