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Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors
Abnormal activation of FGFR signaling pathway plays an essential role in various types of tumors. Therefore, targeting FGFRs represents an attractive strategy for cancer therapy. Herein, we report a series of 1H-pyrrolo[2,3-b]pyridine derivatives with potent activities against FGFR1, 2, and 3. Among...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033946/ https://www.ncbi.nlm.nih.gov/pubmed/35479379 http://dx.doi.org/10.1039/d1ra02660g |
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author | Su, Xingping Liu, Zhihao Yue, Lin Wu, Xiuli Wei, Wei Que, Hanyun Ye, Tinghong Luo, Yi Zhang, Yiwen |
author_facet | Su, Xingping Liu, Zhihao Yue, Lin Wu, Xiuli Wei, Wei Que, Hanyun Ye, Tinghong Luo, Yi Zhang, Yiwen |
author_sort | Su, Xingping |
collection | PubMed |
description | Abnormal activation of FGFR signaling pathway plays an essential role in various types of tumors. Therefore, targeting FGFRs represents an attractive strategy for cancer therapy. Herein, we report a series of 1H-pyrrolo[2,3-b]pyridine derivatives with potent activities against FGFR1, 2, and 3. Among them, compound 4h exhibited potent FGFR inhibitory activity (FGFR1–4 IC(50) values of 7, 9, 25 and 712 nM, respectively). In vitro, 4h inhibited breast cancer 4T1 cell proliferation and induced its apoptosis. In addition, 4h also significantly inhibited the migration and invasion of 4T1 cells. Furthermore, 4h with low molecular weight would be an appealing lead compound which was beneficial to the subsequent optimization. In general, this research has been developing a class of 1H-pyrrolo[2,3-b]pyridine derivatives targeting FGFR with development prospects. |
format | Online Article Text |
id | pubmed-9033946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90339462022-04-26 Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors Su, Xingping Liu, Zhihao Yue, Lin Wu, Xiuli Wei, Wei Que, Hanyun Ye, Tinghong Luo, Yi Zhang, Yiwen RSC Adv Chemistry Abnormal activation of FGFR signaling pathway plays an essential role in various types of tumors. Therefore, targeting FGFRs represents an attractive strategy for cancer therapy. Herein, we report a series of 1H-pyrrolo[2,3-b]pyridine derivatives with potent activities against FGFR1, 2, and 3. Among them, compound 4h exhibited potent FGFR inhibitory activity (FGFR1–4 IC(50) values of 7, 9, 25 and 712 nM, respectively). In vitro, 4h inhibited breast cancer 4T1 cell proliferation and induced its apoptosis. In addition, 4h also significantly inhibited the migration and invasion of 4T1 cells. Furthermore, 4h with low molecular weight would be an appealing lead compound which was beneficial to the subsequent optimization. In general, this research has been developing a class of 1H-pyrrolo[2,3-b]pyridine derivatives targeting FGFR with development prospects. The Royal Society of Chemistry 2021-06-09 /pmc/articles/PMC9033946/ /pubmed/35479379 http://dx.doi.org/10.1039/d1ra02660g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Su, Xingping Liu, Zhihao Yue, Lin Wu, Xiuli Wei, Wei Que, Hanyun Ye, Tinghong Luo, Yi Zhang, Yiwen Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title | Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title_full | Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title_fullStr | Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title_full_unstemmed | Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title_short | Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
title_sort | design, synthesis and biological evaluation of 1h-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033946/ https://www.ncbi.nlm.nih.gov/pubmed/35479379 http://dx.doi.org/10.1039/d1ra02660g |
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