Academic Journal
The Highly Potent AhR Agonist Picoberin Modulates Hh-Dependent Osteoblast Differentiation
| العنوان: | The Highly Potent AhR Agonist Picoberin Modulates Hh-Dependent Osteoblast Differentiation |
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| المؤلفون: | 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 |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2022 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| الوصف: | 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. ; Open access funded by Max Planck Society. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 0022-2623 |
| Relation: | Journal of medicinal chemistry, vol. 65(24), p. 16268-16289; https://hdl.handle.net/10216/158839 |
| DOI: | 10.1021/acs.jmedchem.2c00956 |
| الاتاحة: | https://hdl.handle.net/10216/158839 https://doi.org/10.1021/acs.jmedchem.2c00956 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B66B4DCF |
| قاعدة البيانات: | BASE |
| تدمد: | 00222623 |
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| DOI: | 10.1021/acs.jmedchem.2c00956 |