Journal ArticleDOI
Tubulin colchicine binding site inhibitors as vascular disrupting agents in clinical developments.
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TLDR
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.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.read more
Citations
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TL;DR: It is demonstrated that compound 4a significantly overcame clinically relevant multidrug resistance in a paclitaxel resistant PC-3/TxR prostate cancer xenograft model and was accompanied by elevated levels of apoptosis and disruption of tumor vasculature.
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Tubulin inhibitors as novel anticancer agents: an overview on patents (2013-2018).
TL;DR: This review mainly focuses on the tubulin inhibitors that are being synthesized and studied in cancer research along with their structures and their phases of development in preclinical and clinical research.
References
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TL;DR: It is demonstrated that within minutes of endothelial cell exposure to CA-4-P, myosin light chain (MLC) was phosphorylated, leading to actinomyosin contractility, assembly of actin stress fibers, and formation of focal adhesions, and a Rho-dependent increase in monolayer permeability to dextrans.
Journal Article
Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study.
TL;DR: Available analogs were examined for antimitotic and cytotoxic activity and for effects on tubulin polymerization and colchicine binding and the most promising compound is the (cis)-stilbene derivative ( cis)-1-(3,4,5-trimethoxyphenyl)-2-(3'-hydroxy-4'-methoxyl)ethene, which has been named combretastatin A-4.
Journal Article
Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents
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