Title:Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments
Volume: 22
Issue: 11
Author(s): Ya-Ting Ji, Yan-Na Liu and Zhao-Peng Liu
Affiliation:
Keywords:
Anticancer, antitumor, antivascular, clinical trials, colchicine binding site, tubulin inhibitors, vascular disrupting
agents (VDAs).
Abstract: Tumor vasculature is an important target in cancer treatment. Two distinct vasculartargeting
therapeutic strategies are applied to attack cancer cells indirectly. The antiangiogenic approach
intervenes in the neovascularization processes and blocks the formation of new blood vessels,
while th e antivascular approach targets the established tumor blood vessels, making vascular shutdown
and resulting in rapid haemorrhagic necrosis and tumor cell death. A number of compounds with
diverse structural scaffolds have been designed to target tumor vasculature and they are called vascular
disrupting agents (VDAs). The biological or ligand-directed VDAs utilize antibodies, peptides or
growth factors to deliver toxins or pro-coagulants or proapoptotic affectors to tumor-related blood vessels, while the
small-molecule VDAs selectively target tumor blood vessels and have little effects on the normal endothelium. Among
the small-molecule VDAs, the tubulin colchicine binding site inhibitors have been extensively studied and many of them
have entered the clinical trials, including CA-4P, CA-1P, AVE8062, OXi4503, CKD-516, BNC105P, ABT-751, CYT-
997, ZD6126, NPI-2358, MN-029 and EPC2407. This review makes a summary of the small-molecule VDAs in clinical
developments and highlights some potential VDA leads or candidates for the treatment of tumors.
