PuSH - Publication Server of Helmholtz Zentrum München

Nowacki, M.* ; Cardoso Micu Menezes, F.M. ; Dağdeviren, B.* ; Ballabio, F. ; Napolitano, V. ; Krishna, C.K.* ; Kalel, V.C.* ; Erdmann, R.* ; Sattler, M. ; Popowicz, G.M. ; Dawidowski, M.*

Dibenzo[b,f]azocin-6(5H)-ones and benzo[b]pyrido[2,3-f]azocin-5(6H)-ones: Useful scaffolds for development of protein–protein interaction inhibitors.

Int. J. Mol. Sci. 27:7998 (2026)
Publ. Version/Full Text DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Modulation of protein–protein interactions (PPIs) by small molecules is a vital strategy in drug discovery. Nevertheless, due to the inherent nature of PPI interfaces, practical implementation of this approach remains a high-hanging fruit in medicinal chemistry. In this report, we develop a new line of PEX14–PEX5 PPI inhibitors by homologation of a previously developed dibenzo[b,e]azepin-6(6H)-one scaffold. The challenging chemistry of 8-membered ring formation led to the development of novel PEX14 inhibitors featuring a 6+8+6 tricyclic system. The obtained analogs were tested for their capability of disrupting the PEX5-TbPEX14 PPI, as well as for in vitro activity against the T. brucei protist. Overall, the developed scaffold not only represents an interesting alternative for prospective trypanocidal TbPEX14 ligands but may also be useful in the design of inhibitors of other PPIs mediated by a similar topology of hydrophobic binding pockets.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Drug Discovery ; Small Molecule ; Scaffold ; Drug Development ; Drug ; In Vitro ; Tricyclic; Pex14; Discovery; Import
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Journal International Journal of Molecular Sciences
Quellenangaben Volume: 27, Issue: 18, Pages: , Article Number: 7998 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Ruhr University Bochum, InnovationsFoRUM
Narodowe Centrum Nauki
Deutsche Forschungsge-meinschaft
Bundesministerium fr Bildung und Forschung