Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos
Angiogenesis is a fundamental developmental process and a hallmark of cancer progression. Receptor tyrosine kinases (RTK) are targets for cancer therapy which may include their action as anti-angiogenic agents. Derazantinib (DZB) is an inhibitor of the fibroblast growth factor receptors (FGFRs) 1–3...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/1/25 |
| _version_ | 1797543083726864384 |
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| author | Maria P. Kotini Felix Bachmann Jochen Spickermann Paul M. McSheehy Markus Affolter |
| author_facet | Maria P. Kotini Felix Bachmann Jochen Spickermann Paul M. McSheehy Markus Affolter |
| author_sort | Maria P. Kotini |
| collection | DOAJ |
| description | Angiogenesis is a fundamental developmental process and a hallmark of cancer progression. Receptor tyrosine kinases (RTK) are targets for cancer therapy which may include their action as anti-angiogenic agents. Derazantinib (DZB) is an inhibitor of the fibroblast growth factor receptors (FGFRs) 1–3 as well as other kinase targets including vascular endothelial growth factor receptor 2 (VEGFR2), colony stimulating factor-1 receptor (CSF1R) and platelet-derived growth factor beta receptor (PDGFRbeta). This study aimed to investigate the effect of DZB on blood vessel morphogenesis and to compare its activity to known specific FGFR and VEGFR inhibitors. For this purpose, we used the developing vasculature in the zebrafish embryo as a model system for angiogenesis in vivo. We show that DZB interferes with multiple angiogenic processes that are linked to FGF and VEGF signalling, revealing a potential dual role for DZB as a potent anti-angiogenic treatment. |
| first_indexed | 2024-03-10T13:39:40Z |
| format | Article |
| id | doaj.art-66f58a0a4df54e149eb8a5deb711579d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T13:39:40Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-66f58a0a4df54e149eb8a5deb711579d2023-11-21T03:06:27ZengMDPI AGPharmaceuticals1424-82472020-12-011412510.3390/ph14010025Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish EmbryosMaria P. Kotini0Felix Bachmann1Jochen Spickermann2Paul M. McSheehy3Markus Affolter4Biozentrum der Universität Basel, Klingelbergstrasse 50/70, CH-4053 Basel, SwitzerlandBasilea Pharmaceutica International Ltd., Grenzacherstrasse 487, CH-4005 Basel, SwitzerlandBasilea Pharmaceutica International Ltd., Grenzacherstrasse 487, CH-4005 Basel, SwitzerlandBasilea Pharmaceutica International Ltd., Grenzacherstrasse 487, CH-4005 Basel, SwitzerlandBiozentrum der Universität Basel, Klingelbergstrasse 50/70, CH-4053 Basel, SwitzerlandAngiogenesis is a fundamental developmental process and a hallmark of cancer progression. Receptor tyrosine kinases (RTK) are targets for cancer therapy which may include their action as anti-angiogenic agents. Derazantinib (DZB) is an inhibitor of the fibroblast growth factor receptors (FGFRs) 1–3 as well as other kinase targets including vascular endothelial growth factor receptor 2 (VEGFR2), colony stimulating factor-1 receptor (CSF1R) and platelet-derived growth factor beta receptor (PDGFRbeta). This study aimed to investigate the effect of DZB on blood vessel morphogenesis and to compare its activity to known specific FGFR and VEGFR inhibitors. For this purpose, we used the developing vasculature in the zebrafish embryo as a model system for angiogenesis in vivo. We show that DZB interferes with multiple angiogenic processes that are linked to FGF and VEGF signalling, revealing a potential dual role for DZB as a potent anti-angiogenic treatment.https://www.mdpi.com/1424-8247/14/1/25angiogenesisanastomosisvascular developmentderazantinibFGFR-signallingVEGFR-signalling |
| spellingShingle | Maria P. Kotini Felix Bachmann Jochen Spickermann Paul M. McSheehy Markus Affolter Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos Pharmaceuticals angiogenesis anastomosis vascular development derazantinib FGFR-signalling VEGFR-signalling |
| title | Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos |
| title_full | Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos |
| title_fullStr | Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos |
| title_full_unstemmed | Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos |
| title_short | Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos |
| title_sort | probing the effects of the fgfr inhibitor derazantinib on vascular development in zebrafish embryos |
| topic | angiogenesis anastomosis vascular development derazantinib FGFR-signalling VEGFR-signalling |
| url | https://www.mdpi.com/1424-8247/14/1/25 |
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