Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium is a microtubule destabilizing drug, a water-soluble prodrug of combretasain A4(CA4) and a tumor vascular-targeting agent.

Microtubule is the cylindrical and filamentous structure that required for cell shape, migration, cilia and flagella mobility etc. Tubulin is the major component of microtubules

In proliferative endothelial cells, CA4P (dose less than 1/10 of the max. tolerated dose) leaded to tumor vascular shutdown, and short drug exposure of CA4P caused significant long-term anti-proliferative and cytotoxic effects. [1] In CA40 treated endothelia cell, myosin light chain was phosphorylated and lead to actinomyosin contractility, assembly of actin stress fibers and focal adhesions formation. [2] In HUVEC cells, CA4P blocked growth factor–induced endothelial cell proliferation and migration and impaired capillary tube formation. [3]

In C57BL/6 mice, CA4P treatment in combination with mAb against VE-cardherin facilitated B16 melanoma tumor necrosis and inhibited tumor neoangionesis. [3] In human breast cancer models in vivo, 6 hours after CA4P administration showed a 93% decreased functional vascular volume and lasted over the next 12 hours. [1]

References:
[1] Dark GG, Hill SA, Prise VE, Tozer GM, Pettit GR, Chaplin DJ.? Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature.? Cancer Res. 1997 May 15;57(10):1829-34.
[2] Kanthou C, Tozer GM.? The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells.? Blood. 2002 Mar 15;99(6):2060-9.
[3] Vincent L, Kermani P, Young LM, Cheng J, Zhang F, Shido K, Lam G, Bompais-Vincent H, Zhu Z, Hicklin DJ, Bohlen P, Chaplin DJ, May C, Rafii S.? Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling.? J Clin Invest.? 2005 Nov;115(11):2992-3006.