Eicosatetraynoic acid

Eicosatetraynoic acid (ETYA) is a non-metabolizable analog of Arachidonic acid (HY-109590) and also an inhibitor of the lipoxygenase (LOX)/cyclooxygenase (COX) pathway (ID₅₀ = 8 μM and 4 μM). Eicosatetraynoic acid acts as a suicide substrate to inhibit the production of inflammatory mediators such as leukotrienes and prostaglandins. Eicosatetraynoic acid acts directly on cell membranes and membrane proteins to exert a wide range of effects, including blocking potassium channels, increasing cell membrane fluidity, elevating intracellular calcium levels, inhibiting DNA synthesis in tumor cells, inducing differentiation of certain cells, and specifically inhibiting the assembly and replication of orthopoxviruses. Eicosatetraynoic acid alleviates acute lung injury induced by chemicals such as phosgene^{[1][2][3][4][5]}. In Vitro:Eicosatetraynoic acid dose-dependently reduces MDA production in cultured human umbilical vein endothelial cells co-incubated with low-density lipoprotein^[1].
Eicosatetraynoic acid (40 μM; 4-72 h) reversibly inhibits DNA synthesis and blocks the proliferation of PC3, U937 and A172 cells without inducing significant cytotoxicity^[2].
Eicosatetraynoic acid (40 μM; 3-7 d) induces partial monocyte-like differentiation in U937 cells, and induces partial glial-like differentiation in A172 cells after 72 h of incubation; in addition, the differentiation of U937 cells progresses gradually over 5 to 7 days^[2].
Incubation with eicosatetraynoic acid (40 μM; 72 h) for 72 h induces cell type-specific ultrastructural changes, including severe oxidative stress-related mitochondrial damage in PC3 cells, milder damage in A172 cells, and immature monocyte morphology in U937 cells^[2].
Eicosatetraynoic acid (40 μM) rapidly regulates multiple signal transduction pathways in PC3 and U937 cells, including increasing membrane fluidity and intracellular Ca²⁺ levels, inhibiting O₂ uptake, reversibly blocking DNA synthesis, downregulating c-myc, inhibiting eicosanoid synthesis, and altering the localization of protein kinase C^[2].
Eicosatetraynoic acid non-selectively inhibits 12-lipoxygenase (ID₅₀ = 4 μM) and fatty acid cyclooxygenase (ID₅₀ = 8 μM) in washed human platelets^[3].
Eicosatetraynoic acid (79-316 μM) specifically and effectively blocks the replication of orthopoxviruses (vaccinia, vaccinia vaccine, and ectromelia viruses)^[4]. In Vivo:Eicosatetraynoic acid (50-100 µM/200 μL ethanol solution; i.p. or isolated lung perfusion; single administration) exerts antioxidant effects and effectively alleviates pulmonary edema and oxidative damage.
Eicosatetraynoic acid (300 μM; topical administration) significantly reduces pock formation on the chorioallantoic membranes of chicken embryos infected with the vaccinia virus CPV-BR.D1^[4].