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DGK Inhibitors Library

DGK Inhibitors Library

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ChemDiv’s DGK Inhibitors Library contains 12,000 compounds.

Diacylglycerol kinase (DGK or DAGK) is a family of enzymes that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), utilizing ATP. In non-stimulated cells, DGK activity is low, allowing DAG to be used for glycerophospholipid biosynthesis, but on receptor activation of the phosphoinositide pathway, DGK activity increases, driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling molecules with distinct cellular targets, DGK therefore occupies an important position, effectively serving as a switch by terminating the signaling of one lipid while simultaneously activating signaling by another.

DGK is highly expressed in hepatocellular carcinoma and melanoma cells. DGK expression is involved in hepatocellular carcinoma progression and is a positive regulator of the proliferative activity of hepatocellular carcinoma through the Ras/Raf/MEK/ERK pathway. In melanoma cells, DGK positively regulates the tumor necrosis factor-α-dependent nuclear factor-κB (p65) activation via the protein kinase mediated Ser311 phosphorylation of p65. Therefore, the suppression of DGK activity is expected to inhibit the progression of these cancers. [1]

[1] K. Liu et al., “A novel diacylglycerol kinase α -selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response,” J. Lipid Res., vol. 57, no. 3, pp. 368–379, 2016, doi: 10.1194/jlr.M062794.
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