Abstract
Vascular disrupting agents (VDAs) are a new class of potential anticancer drugs that selectively destroy tumor vasculature and shutdown blood supply to solid tumors, causing extensive tumor cell necrosis. VDAs target established tumor blood vessels, which are distinct from antiangiogenic agents that prevent the formation of new blood vessels. There are two types of VDAs, small molecules and ligand-directed agents. Most of the small molecule VDAs are tubulin inhibitors, including CA4P, ZD6126, AVE8062, OXi-4503, NPI-2358, MN-029 and EPC2407. The others are synthetic flavonoids including FAA and DMXAA that induce the production of local cytokines such as TNF-alpha. VDAs have shown good antitumor efficacy in animal models, especially in combination with established anticancer agents. Several VDAs, including CA4P and DMXAA, have demonstrated good safety profile as well as some promising efficacy in phase I clinical trials. Currently CA4P and DMXAA are in phase II clinical trials and AVE8062, OXi-4503, NPI-2358 and MN- 029 are in phase I clinical trials. This review will focus on recent progress in the discovery and development of small molecule VDAs, including recently published patent applications and issued patents related with small molecule VDAs.
Keywords: Vascular disrupting agents (VDAs), anticancer drugs, small molecule, tubulin inhibitors, synthetic flavonoids, CA4P, DMXAA, ZD6126, AVE8062, OXi-4503
Recent Patents on Anti-Cancer Drug Discovery
Title: Small Molecule Vascular Disrupting Agents: Potential New Drugs for Cancer Treatment
Volume: 2 Issue: 1
Author(s): Sui X. Cai
Affiliation:
Keywords: Vascular disrupting agents (VDAs), anticancer drugs, small molecule, tubulin inhibitors, synthetic flavonoids, CA4P, DMXAA, ZD6126, AVE8062, OXi-4503
Abstract: Vascular disrupting agents (VDAs) are a new class of potential anticancer drugs that selectively destroy tumor vasculature and shutdown blood supply to solid tumors, causing extensive tumor cell necrosis. VDAs target established tumor blood vessels, which are distinct from antiangiogenic agents that prevent the formation of new blood vessels. There are two types of VDAs, small molecules and ligand-directed agents. Most of the small molecule VDAs are tubulin inhibitors, including CA4P, ZD6126, AVE8062, OXi-4503, NPI-2358, MN-029 and EPC2407. The others are synthetic flavonoids including FAA and DMXAA that induce the production of local cytokines such as TNF-alpha. VDAs have shown good antitumor efficacy in animal models, especially in combination with established anticancer agents. Several VDAs, including CA4P and DMXAA, have demonstrated good safety profile as well as some promising efficacy in phase I clinical trials. Currently CA4P and DMXAA are in phase II clinical trials and AVE8062, OXi-4503, NPI-2358 and MN- 029 are in phase I clinical trials. This review will focus on recent progress in the discovery and development of small molecule VDAs, including recently published patent applications and issued patents related with small molecule VDAs.
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Cai X. Sui, Small Molecule Vascular Disrupting Agents: Potential New Drugs for Cancer Treatment, Recent Patents on Anti-Cancer Drug Discovery 2007; 2 (1) . https://dx.doi.org/10.2174/157489207779561462
DOI https://dx.doi.org/10.2174/157489207779561462 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
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In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...read more
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