Structure-Activity Relationship Studies of Hydantoin-Cored Ligands for Smoothened Receptor
© 2021 The Authors. Published by Wiley-VCH GmbH..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
ChemistryOpen - 10(2021), 10 vom: 15. Okt., Seite 1028-1032 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.01.2022 Date Revised 03.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/open.202100216 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331889668 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Published by Wiley-VCH GmbH. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a anti-cancer | |
| 650 | 4 | |a halogen bonding | |
| 650 | 4 | |a molecular dynamics | |
| 650 | 4 | |a smoothened receptor | |
| 650 | 4 | |a structural biology | |
| 650 | 7 | |a Hydantoins |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Smoothened Receptor |2 NLM | |
| 700 | 1 | |a Zhou, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Kang |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Dongxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhihao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Cuixia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yueming |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Zhiping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Suwen |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Houchao |e verfasserin |4 aut | |
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