a long terminal solubilizing chain, such as in the structure of nintedanib (48; Fig. 14)
[6, 116, 117].
It is worth mentioning that all approved VEGFR inhibitors in clinical use
(Table 3), and many others in different stages of drug development, present weak
Fig. 13 Simplified signal transduction pathway mediated by VEGF-A binding to VEGFR-2,
inducing receptor dimerization and autophosphorylation of specific intracellular tyrosine residues.
PLC-γ phospholipase C-γ, PKC protein kinase C, eNOS endothelial nitric oxide synthase, NO nitric
oxide, Ras rat sarcoma (it is a small GTPase), Raf rapidly accelerated fibrosarcoma, MEK MAPK/
ERK kinase, ERK extracellular regulated kinases, p38 p38 mitogen-activated protein kinase, HSP27
heat-shock protein 27, PI3K phosphoinositide 3-kinase, PIP3 phosphatidylinositol (3,4,5)trisphosphate, AKT Protein kinase B (PKB) (also known as Akt), mTOR mammalian target of
rapamycin
174
L. M. Lima et al.
[6, 116, 117].
It is worth mentioning that all approved VEGFR inhibitors in clinical use
(Table 3), and many others in different stages of drug development, present weak
Fig. 13 Simplified signal transduction pathway mediated by VEGF-A binding to VEGFR-2,
inducing receptor dimerization and autophosphorylation of specific intracellular tyrosine residues.
PLC-γ phospholipase C-γ, PKC protein kinase C, eNOS endothelial nitric oxide synthase, NO nitric
oxide, Ras rat sarcoma (it is a small GTPase), Raf rapidly accelerated fibrosarcoma, MEK MAPK/
ERK kinase, ERK extracellular regulated kinases, p38 p38 mitogen-activated protein kinase, HSP27
heat-shock protein 27, PI3K phosphoinositide 3-kinase, PIP3 phosphatidylinositol (3,4,5)trisphosphate, AKT Protein kinase B (PKB) (also known as Akt), mTOR mammalian target of
rapamycin
174
L. M. Lima et al.