Autor(es): Flegel, J ; Shaaban, S ; Jia, ZJ ; Schulte, B ; Lian, Y ; Krzyzanowski, A ; Metz, M ; Schneidewind, T ; Wesseler, F ; Flegel, A ; Reich, A ; Brause, A ; Xue, G ; Zhang, M ; Dötsch, L ; Stender, ID ; Hoffmann, Jan-Erik ; Scheel, R ; Janning, P ; Rastinejad, F ; Schade, D ; Strohmann, C ; Antonchick, AP ; Sievers, S ; Moura-Alves, P ; Ziegler, S ; Waldmann, H
Data: 2022
Identificador Persistente: https://hdl.handle.net/10216/158839
Origem: Repositório Aberto da Universidade do Porto
Identification and analysis of small molecule bioactivity in target-agnostic cellular assays and monitoring changes in phenotype followed by identification of the biological target are a powerful approach for the identification of novel bioactive chemical matter in particular when the monitored phenotype is disease-related and physiologically relevant. Profiling methods that enable the unbiased analysis of compound-perturbed states can suggest mechanisms of action or even targets for bioactive small molecules and may yield novel insights into biology. Here we report the enantioselective synthesis of natural-product-inspired 8-oxotetrahydroprotoberberines and the identification of Picoberin, a low picomolar inhibitor of Hedgehog (Hh)-induced osteoblast differentiation. Global transcriptome and proteome profiling revealed the aryl hydrocarbon receptor (AhR) as the molecular target of this compound and identified a cross talk between Hh and AhR signaling during osteoblast differentiation.
