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Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor
An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly co...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515922/ https://www.ncbi.nlm.nih.gov/pubmed/34648230 http://dx.doi.org/10.1002/open.202100216 |
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author | Liu, Yang Zhou, Fang Ding, Kang Xue, Dongxiang Zhu, Zhihao Li, Cuixia Li, Fei Xu, Yueming Xu, Fei Le, Zhiping Zhao, Suwen Tao, Houchao |
author_facet | Liu, Yang Zhou, Fang Ding, Kang Xue, Dongxiang Zhu, Zhihao Li, Cuixia Li, Fei Xu, Yueming Xu, Fei Le, Zhiping Zhao, Suwen Tao, Houchao |
author_sort | Liu, Yang |
collection | PubMed |
description | An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly conservative in chirality, ring size, and substituents. On each benzene at two ends, a plethora of variations, particularly halogen substitutions, were introduced and investigated. Analysis of the structure‐activity relationship revealed miscellaneous halogen effects. The ligands with double halogen substituents exhibit remarkably enhanced potency, providing promising candidates that potentially overcome the common drug resistance and useful heavy‐atom labeled chemical tools for co‐crystallization studies of SMO. |
format | Online Article Text |
id | pubmed-8515922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85159222021-10-21 Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor Liu, Yang Zhou, Fang Ding, Kang Xue, Dongxiang Zhu, Zhihao Li, Cuixia Li, Fei Xu, Yueming Xu, Fei Le, Zhiping Zhao, Suwen Tao, Houchao ChemistryOpen Communications An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly conservative in chirality, ring size, and substituents. On each benzene at two ends, a plethora of variations, particularly halogen substitutions, were introduced and investigated. Analysis of the structure‐activity relationship revealed miscellaneous halogen effects. The ligands with double halogen substituents exhibit remarkably enhanced potency, providing promising candidates that potentially overcome the common drug resistance and useful heavy‐atom labeled chemical tools for co‐crystallization studies of SMO. John Wiley and Sons Inc. 2021-10-14 /pmc/articles/PMC8515922/ /pubmed/34648230 http://dx.doi.org/10.1002/open.202100216 Text en © 2021 The Authors. Published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Communications Liu, Yang Zhou, Fang Ding, Kang Xue, Dongxiang Zhu, Zhihao Li, Cuixia Li, Fei Xu, Yueming Xu, Fei Le, Zhiping Zhao, Suwen Tao, Houchao Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title | Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title_full | Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title_fullStr | Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title_full_unstemmed | Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title_short | Structure‐Activity Relationship Studies of Hydantoin‐Cored Ligands for Smoothened Receptor |
title_sort | structure‐activity relationship studies of hydantoin‐cored ligands for smoothened receptor |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515922/ https://www.ncbi.nlm.nih.gov/pubmed/34648230 http://dx.doi.org/10.1002/open.202100216 |
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