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. 2015 Aug 27;10:89–98. doi: 10.2147/CE.S82905

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© 2015 Inomata et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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Chemical structure of nintedanib.

Notes: Indolinone lead compounds substituted at position 6 were selected by assessing inhibition of tumor angiogenesis and shown to inhibit VEGFR-2. Derivatives of the lead compound were further screened to enhance triple angiokinase (VEGFR-2, FGFR-1, and PDGFR-α) inhibitory activity. Two compounds, BIBF1000 and BIBF1120, were tested in assays of antitumor activity, and BIBF1120 was selected for clinical trials.

Abbreviations: VEGFR, vascular endothelial growth factor receptor; FGFR, fibroblast growth factor receptor; PDGFR, platelet-derived growth factor receptor.