微管蛋白-秋水仙碱结合位点作为血管损伤抑制剂的临床研究进展

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:

关键词: 抗癌，抗癌，抗血管，临床试验，秋水仙碱结合位点，微管蛋白抑制剂，血管裂解剂

摘要: 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.

Cite this article as:

Ya-Ting Ji, Yan-Na Liu and Zhao-Peng Liu , Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments, Current Medicinal Chemistry 2015; 22 (11) . https://dx.doi.org/10.2174/0929867322666150114163732