scholarly journals Design, Synthesis and Biological Evaluation of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-Substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

2016 ◽  
Author(s):  
Zhen Zhang ◽  
Dongmei Zhao ◽  
Yang Dai ◽  
Maosheng Cheng ◽  
Meiyu Geng ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Fibroblast Growth ◽  
Design Synthesis ◽  
Promising Target ◽  
Cancer Types ◽  
Synthesis And Biological Evaluation

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold

2015 ◽  
Vol 13 (28) ◽  
pp. 7643-7654 ◽  
Author(s):  
Jian Liu ◽  
Xia Peng ◽  
Yang Dai ◽  
Wei Zhang ◽  
Sumei Ren ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Therapy ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Fibroblast Growth ◽  
Design Synthesis ◽  
Potential Target ◽  
Synthesis And Biological Evaluation

Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy.

scholarly journals Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

2020 ◽  
Author(s):  
Matthias Haase ◽  
Anne Thiel ◽  
Ute I. Scholl ◽  
Hany Ashmawy ◽  
Matthias Schott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adrenocortical Carcinoma ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Beta Catenin ◽  
Fibroblast Growth ◽  
Mutational Status ◽  
Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR) 2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

scholarly journals Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

2020 ◽  
Author(s):  
Matthias Haase ◽  
Anne Thiel ◽  
Ute I. Scholl ◽  
Hany Ashmawy ◽  
Matthias Schott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adrenocortical Carcinoma ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Beta Catenin ◽  
Fibroblast Growth ◽  
Mutational Status ◽  
Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

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