Tools
Tools
Flegel, J., Shaaban, S., Jia, Z.J., 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, I.D., Hoffmann, J.-E., Scheel, R., Janning, P., Rastinejad, F., Schade, D., Strohmann, C., Antonchick, A.P. 
ORCID: 0000-0003-0435-9443, Sievers, S., Moura-Alves, P., Ziegler, S. and Waldmann, H.,
2022.
The highly potent AhR agonist picoberin modulates Hh-dependent osteoblast differentiation.
Journal of Medicinal Chemistry, 65 (24), pp. 16268-16289.
ISSN 0022-2623
|
Text
1631731_Antonchick.pdf - Published version Download (8MB) | Preview |
Abstract
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.
| Item Type: | Journal article | ||||||
|---|---|---|---|---|---|---|---|
| Publication Title: | Journal of Medicinal Chemistry | ||||||
| Creators: | Flegel, J., Shaaban, S., Jia, Z.J., 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, I.D., Hoffmann, J.-E., Scheel, R., Janning, P., Rastinejad, F., Schade, D., Strohmann, C., Antonchick, A.P., Sievers, S., Moura-Alves, P., Ziegler, S. and Waldmann, H. | ||||||
| Publisher: | American Chemical Society (ACS) | ||||||
| Date: | 22 December 2022 | ||||||
| Volume: | 65 | ||||||
| Number: | 24 | ||||||
| ISSN: | 0022-2623 | ||||||
| Identifiers: |
|
||||||
| Rights: | Copyright © 2022 The Authors. Published by American Chemical Society. Open access funded by Max Planck Society. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Linda Sullivan | ||||||
| Date Added: | 11 Jan 2023 10:45 | ||||||
| Last Modified: | 11 Jan 2023 10:45 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/47804 |
Actions (login required)
 |
Edit View |
Views
Views per month over past year
Downloads
Downloads per month over past year
