Chemical Synthesis of Lipid Mediator 22-HDoHE and Structural Analogs
Anti-angiogenic and anti-tumor activity in vitro and in vivo Potentially fewer side-effects Chemical synthesis
Inhibit tumor growth, angiogenesis, and lymphangiogenesis
Although effective, current FDA approved angiogenesis inhibitors to treat angiogenic diseases, like macular degeneration, or to inhibit tumor growth in cancer have various limitations. Several of these drugs, which utilize synthetic compounds, are associated with adverse side effects such as issues with wound healing, heart and kidney function, fetal development, and reproduction. In some cases the effects can include problems with bleeding, clots in the arteries (resulting in stroke or heart attack), hypertension, and protein in the urine. Researchers at the University of California, Davis have developed a method to chemically synthesize the natural endogenous lipid mediator, 22-hydroxydocosahexaenoic acid (22-HDoHE), with demonstrated anti-angiogenic and anti-tumor activity. 22-HDoHE is an endogenous ω-hydroxylated polyunsaturated fatty acid (PUFA) produced by cytochrome P450 omega-hydroxylase enzyme. Because it occurs in many tissues such as brain, lung, kidney and liver tissue, it has demonstrated anti-angiogenic activity in primary endothelial cells and can inhibit tumor growth in vivo. In addition, 22-HDoHE is endogenously present in the human body, meaning that this compound or its structural analogs has the potential to produce less adverse side-effects.
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