Description: Fosbretabulin tromethamine, the tromethamine salt of Fosbretabulin (CA4P; Zybrestat), is a natural cis-stilbene analog acting as a tubulin inhibitor. It is the water-soluble prodrug of CA-4. It that has to be activated to the active form, Combretastatin A4 (CA4), which is a highly potent MTA (microtubule-targeting agent) or tubulin inhibitor that acts as a potent anticancer agent that binds β-tubulin with a Kd of 0.4 μM in a cell-free assay. Fosbretabulin was originally isolated from African tree Combretum caffrum. Combretastatin A4 inhibits the polymerization of tubulin with an IC50 of 2.4 μM, and also disrupts tumor vasculature. Under in vivo conditions, the prodrug fosbretabulin is dephosphorylated and activated to its active form, combretastatin A4, which binds to tubulin dimers and prevents microtubule polymerization, resulting in mitotic arrest and apoptosis in endothelial cells.

References: Br J Cancer. 1995 Apr;71(4):705-11; Cancer Res. 1997 May 15;57(10):1829-34.