Vascular endothelial growth factor receptor 2 and Beta-tubulin (VEGFR-2/β-tubulin)

The dual target comprising Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) and beta-tubulin represents a synergistic pharmacological strategy in oncology. VEGFR-2 is a primary receptor tyrosine kinase that mediates the effects of VEGF, driving the proliferation, migration, and survival of endothelial cells to form new blood vessels (UniProt P35968). Beta-tubulin is a fundamental structural component of microtubules, which are essential for maintaining the cytoskeleton of endothelial cells and forming the mitotic spindle during cell division (UniProt P07437). By simultaneously targeting these two proteins, therapeutic agents can exert a 'dual-action' effect: inhibiting the formation of new vessels (anti-angiogenic) while rapidly destabilizing and destroying existing tumor vasculature (vascular disruption). This approach is particularly effective in solid tumors where it can cause rapid tumor necrosis and overcome resistance associated with single-target anti-angiogenic therapies (PMID: 31446244). Drugs like BNC105P and various combretastatin derivatives are designed to exploit this dual mechanism to enhance clinical efficacy (PMID: 30316144).

Other names

VEGFR2 and Tubulin beta chainKDR and TUBBFlk-1 and Beta-tubulinKinase insert domain receptor and Tubulin

Dual inhibition involving the blockade of VEGFR-2 tyrosine kinase activity to prevent new blood vessel formation (anti-angiogenesis) and the inhibition of beta-tubulin polymerization to disrupt existing tumor vasculature (vascular disruption) and induce mitotic arrest.