fosbretabulin

Fosbretabulin is a synthetic, water-soluble, phosphorylated prodrug of the natural product combretastatin A4, originally isolated from the African bush willow (Combretum caffrum)[1][3][7]. It acts as a vascular disrupting agent (VDA) and microtubule destabilizer. After administration, it is dephosphorylated in vivo to its active metabolite, combretastatin A4. This active form binds to tubulin dimers and inhibits microtubule polymerization in endothelial cells of tumor vasculature[1][3][6]. The resulting mitotic arrest and apoptosis lead to collapse of tumor blood vessels and central necrosis of tumors. Fosbretabulin also disrupts cell–cell adhesion mediated by vascular endothelial-cadherin (VE-cadherin), further contributing to vascular disruption[5][6]. It has been investigated primarily for anaplastic thyroid cancer but also for other solid tumors including neuroendocrine tumors[2][5][7].

Brand names

fosbretabulin

Other names

combretastatin A-4 phosphatephosbretabulin