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technologyanti-angiogenesis
Angiogenesis is the process through which new blood vessels are formed. While angiogenesis is normal in growth, development and wound repair, tumors cells also need new blood vessels in order to grow and spread. Drugs are needed that can selectively inhibit tumor vascularization in cancer and other neovascular diseases.
TM601 Anti-Angiogenic Activity
TM601 has been shown in well established models such as the chick egg model, the mouse matrigel plug assay and the mouse choroidal neovascularization model, to inhibit new blood vessel formation. TM601 interacts with, a protein over-expressed on the surface of cancer and endothelial cells and causes anti-angiogenic effects on new-blood vessel growth. In research to date, TM601 has been shown to:
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inhibit new blood vessel growth by blocking several angiogenesis stimulating pathways in the chick egg model; |
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inhibit angiogenesis in mouse matrigel plug model with systemic delivery of TM601; |
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effectively inhibit neovascularization in two models of ocular neovascularization; and |
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act synergistically with anti-VEGF therapeutic targets in the chick egg model. |
Evidence of Anti-Angiogenic Effects of TM601 in Standard Models
The CAM assay, a chick egg model, is a commonly used model for angiogenesis in cancer biology and ophthalmology. In these studies, eight pro-angiogenic factors which act by distinct mechanisms were shown to be effectively inhibited by TM601. The figures below demonstrate the ability of TM601 to potently inhibit angiogenesis in the CAM assay.
Angiogenesis Inhibition in the CAM Assay
Further research in the CAM assay shows that TM601 has a similar anti-angiogenic effects as the anti-VEGF antibody agents Avastin and Lucentis. Additionally in drug combination studies, TM601 appears to act synergistically with both Avastin and Lucentis.
Angiogenesis Inhibition
Legend. A - Using a variety of compounds to stimulate neovascularization of the developing chick egg, TM601 was found to potently inhibit formation of blood-vessel branch points. Inhibition of a broad range of angiogenic stimuli suggests that TM601 could affect multiple pathways. B - In the chorioallantoic membrane (CAM) assay, TM601 decreases VEGF-stimulated neovascularization at doses similar to effective concentrations of Avastin and Lucentis.
Summary of Anti-Angiogenic Effects of TM601 in Standard Models
| Model | Results |
| Chorio- Allantoic Membrane (CAM) Model |
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| Mouse Matrigel Plug |
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| Eye Models |
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For more information publications related to this research, please click here.