Vascular endothelial growth factor receptor 1 and Vascular endothelial growth factor receptor 3 (VEGFR1/VEGFR3)

Vascular endothelial growth factor receptor 1 (VEGFR1) and Vascular endothelial growth factor receptor 3 (VEGFR3) are essential receptor tyrosine kinases (RTKs) that govern the formation and maintenance of the blood and lymphatic vascular systems (Source [1], [11]). VEGFR1, also known as Flt-1, binds ligands such as VEGF-A, VEGF-B, and placental growth factor (PlGF), playing a complex role as both a decoy receptor and a signaling mediator in angiogenesis and inflammation (Source [6], [18]). VEGFR3, or Flt-4, is the primary driver of lymphangiogenesis, responding to VEGF-C and VEGF-D to regulate lymphatic vessel development and function (Source [2], [17]). In pathological contexts, particularly oncology, these receptors are frequently overexpressed to promote tumor-associated angiogenesis and lymphangiogenesis, facilitating tumor growth and metastatic spread (Source [7], [16]). Many clinically approved multi-kinase inhibitors, such as sunitinib, axitinib, and lenvatinib, target the intracellular kinase domains of both VEGFR1 and VEGFR3 to inhibit these pathological processes (Source [3], [13]). However, the systemic inhibition of these receptors can lead to significant adverse effects, including hypertension and proteinuria, reflecting their vital roles in normal physiological vascular homeostasis (Source [10], [16]).

Other names

Flt-1/Flt-4VEGFR-1/VEGFR-3Vascular endothelial growth factor receptor 1/3Fms-like tyrosine kinase 1 and 4

Inhibition of the intracellular tyrosine kinase domains of VEGFR1 and VEGFR3, which prevents ligand-induced autophosphorylation and blocks downstream signaling pathways such as MAPK/ERK and PI3K/Akt, leading to the suppression of angiogenesis and lymphangiogenesis (Source [1], [3], [17]).