Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 3, Platelet-derived growth factor receptor beta, Protein tyrosine kinase 6, and TEK receptor tyrosine kinase (VEGFR1/3, PDGFRβ, PTK6, TEK)

This target profile represents a group of tyrosine kinases, primarily receptor tyrosine kinases (RTKs), that play critical roles in regulating angiogenesis, lymphangiogenesis, and cellular proliferation. The group includes Vascular Endothelial Growth Factor Receptors 1 and 3 (VEGFR1, VEGFR3), which are essential for the formation of blood and lymphatic vessels, and Platelet-Derived Growth Factor Receptor beta (PDGFRβ), which mediates pericyte recruitment and vascular stability. Additionally, it includes TEK (also known as TIE2), a receptor involved in vascular maturation, and Protein Tyrosine Kinase 6 (PTK6, also known as BRK), a non-receptor kinase often overexpressed in various cancers. These kinases are frequently dysregulated in malignancies, promoting tumor growth, survival, and metastasis through the recruitment of new blood vessels and direct mitogenic signaling. Drugs targeting this multi-kinase profile, such as vorolanib and regorafenib, are designed to simultaneously inhibit multiple pathways of tumor progression, offering a comprehensive anti-angiogenic and anti-tumor strategy. However, the broad inhibition of these essential signaling pathways can lead to systemic side effects, including hypertension and impaired wound healing.

Other names

VEGFR1VEGFR3PDGFRBPTK6TEKFLT1FLT4BRKTIE2CD140bCD202bFms-like tyrosine kinase 1Fms-like tyrosine kinase 4Breast tumor kinasePlatelet-derived growth factor receptor betaVascular endothelial growth factor receptor 1Vascular endothelial growth factor receptor 3

Competitive inhibition of the ATP-binding site of the kinase domain, preventing autophosphorylation and downstream signaling.