Product Code Database
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through drugs or diet.
While angiogenesis is a critical part of wound healing and other favorable processes, certain types of angiogenesis are associated with the growth of malignant tumors. Thus angiogenesis inhibitors have been closely studied for possible cancer treatment. Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but the limitations of anti-angiogenic therapy have been shown in practice. Currently, angiogenesis inhibitors are recognized for their improvement of cancer immunotherapyFukumura, D., et al., Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol, 2018. 15(5): p. 325-340. doi: 10.1038/nrclinonc.2018.29Huinen, Z., et al., Anti-angiogenic agents - overcoming tumor endothelial cell anergy and improving immunotherapy outcomes. Nat. Rev. Clin. Oncol., 2021. 18(8): p. 527-540. doi: 10.1038/s41571-021-00496-y by overcoming endothelial cell anergy. Angiogenesis inhibitors are also used to effectively treat macular degeneration in the eye, and other diseases that involve a proliferation of blood vessels.Dudley, A.C. & Griffioen, A.W., Pathological angiogenesis: mechanisms and therapeutic strategies. Angiogenesis, 2023. doi: 10.1007/s10456-023-09876-7Cancer.com homepage. National Cancer Institute at the National Institutes of Health; 2011 cited. Available from:
During tumor growth, the action of angiogenesis stimulators surpasses the control of angiogenesis inhibitors, allowing for unregulated or less regulated blood vessel growth and formation. Endogenous inhibitors are attractive targets for cancer therapy because they are less toxic and less likely to lead to drug resistance than some exogenous inhibitors. However, the therapeutic use of endogenous inhibitors has disadvantages. In animal studies, high doses of inhibitors were required to prevent tumor growth and the use of endogenous inhibitors would likely be long-term.
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for VEGF-B and PIGF |
| antagonist of angiopoietin 1 |
| inhibit cell migration, cell proliferation, cell adhesion and survival of Endothelium |
| inhibit cell proliferation and induce apoptosis of endothelial cells |
| inhibit cell migration, cell proliferation and survival of endothelial cells |
| inhibit cell proliferation of endothelial cells |
| inhibits binding of bFGF and VEGF |
| inhibit cell migration of endothelial cells |
| inhibit cell migration of endothelial cells, downregulate bFGF |
| inhibit cell proliferation of endothelial cells |
| VEGF |
| affects cell proliferation of endothelial cells |
| inhibit binding and activity of VEGF |
| inhibit integrin signalling |
| inhibits proteases |
| inhibits endothelial cell migration, induces apoptosis |
| mannose 6-phosphate binding lysosomal protein |
A recent method for the delivery of anti-angiogenesis factors to tumor regions in cancer patients uses genetically modified bacteria that are able to colonize solid tumors in vivo, such as Clostridium, Bifidobacteria and Salmonella by adding genes for anti-angiogenic factors such as endostatin or IP10 chemokine and removing any harmful virulence genes. A target can also be added to the outside of the bacteria so that they are sent to the correct organ in the body. The bacteria can then be injected into the patient and they will locate themselves to the tumor site, where they release a continual supply of the desired drugs in the vicinity of a growing cancer mass, preventing it from being able to gain access to oxygen and ultimately starving the cancer cells.Gardlik, R., Behuliak, M., Palffy, R., Celec, P., & Li, C. J. (2011). Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy. Gene therapy, 18(5), 425-431. This method has been shown to work both in vitro and in vivo in mice models, with very promising results.Xu, Y. F., Zhu, L. P., Hu, B., Fu, G. F., Zhang, H. Y., Wang, J. J., & Xu, G. X. (2007). A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy. Cancer gene therapy, 14(2), 151-157. It is expected that this method will become commonplace for treatment of various cancer types in humans in the future.
In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as anti-obesity agents, as blood vessels in adipose tissue never fully mature, and are thus destroyed by angiogenesis inhibitors. Angiogenesis inhibitors are also used as treatment for the wet form of macular degeneration. By blocking VEGF, inhibitors can cause regression of the abnormal blood vessels in the retina and improve vision when injected directly into the vitreous humor of the eye.
| VEGF | |
| inhibits VEGFR phosphorylation, glycosylation, mTOR signaling, endothelial cell proliferation, cell migration, lumen formation, and tumor associated angiogenesis. | |
| Methionine aminopeptidase 2 inhibitors, inhibit cell proliferation and cell migration of endothelial cells | |
| TNP-470 (an analog of fumagillin) | |
| activate immune system | |
| downregulate angiogenesis stimulators and inhibit cell migration of endothelial cells | |
| stimulate angiogenesis inhibitor formation | |
| inhibits binding of angiogenesis stimulators | |
| suramin | |
| SU5416 | |
| thrombospondin | |
| VEGFR antagonists | |
| inhibit basement membrane degradation | |
| Cartilage-Derived Angiogenesis Inhibitory Factor | |
| matrix metalloproteinase inhibitors | |
| inhibit cell proliferation and induce apoptosis of endothelial cells | |
| inhibit cell migration, cell proliferation and survival of endothelial cells | |
| inhibit cell proliferation and cell migration and induce apoptosis of endothelial cells | |
| inhibit cell proliferation of endothelial cells | |
| copper chelation which inhibits blood vessel growth | |
| inhibit cell proliferation of endothelial cells | |
| inhibit cell migration, cell proliferation, cell adhesion and survival of endothelial cells | |
| VEGF | |
| induce apoptosis of endothelial cells | |
| inhibit cell migration of endothelial cells | |
| ramucirumab | inhibition of VEGFR2 Ramucirumab (Cyramza) package insert |
| Unknown | |
| VEGF | |
| inhibit kinases | |
After a series of clinical trials in 2004, Avastin was approved by the FDA, becoming the first commercially available anti-angiogenesis drug. FDA approval of Avastin for breast cancer treatment was later revoked on November 18, 2011.
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