[CAS NO. 168555-66-6]  Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium

Fosbretabulin disodium (Combretastatin A-4 phosphate disodium, CA4P disodium) is the water-soluble prodrug of combretastatin A4 (CA4), which is originally isolated from African tree . CA4 is a tubulin-binding agent that binds at or near the colchicine binding site of β-tubulin (Kd = 0.40 μM), inhibits tubulin assembly with IC50 of 2.4 μM. CA4 is cytotoxic towards proliferating but not quiescent endothelial cells, has potent and selective toxicity towards tumor vasculature. CA4P (1 mM, 30 minutes) disrupts the endothelial microtubule cytoskeleton and mediates changes in endothelial cell morphology. CA4P stimulates actin stress fiber formation and membrane blebbing and increases monolayer permeability via Rho/Rho-kinase. CA4P increases endothelial cell permeability, while inhibiting endothelial cell migration and capillary tube formation predominantly through disruption of VE-cadherin/β-catenin/Akt signaling pathway, thereby leading to rapid vascular collapse and tumor necrosis.