Description
R-59-949 is an inhibitor of diacylglycerol kinase α (DGK-α) with an IC
50 value of 300 nM in isolated platelet plasma membranes using exogenous diacylglycerol as a substrate. DGK-α inhibition with R-59-949 increases diacylglycerol-dependent PKC activity, serotonin secretion, and aggregation of thrombin-stimulated platelets. R-59-949 inhibits DGK-α activity induced by platelet-derived growth factor (PDGF) in intact vascular smooth muscle cells (VSMCs). It inhibits high K
+- and glucose-induced insulin secretion in MIN6 pancreatic β-cells in a dose-dependent manner.
In vivo, administration of R-59-949 prevents retinal neovascularization in a mouse model of oxygen-induced retinopathy.
Uses
Diacylglycerol Kinase Inhibitor II has been used to determine tumor-induced inhibition with genetically modified cytotoxic T cells expressing chimeric antigen receptors (CAR). It has also been used to induce pAkt and PKR-like extracellular signal-regulated kinase (pErk) signals in T-cell acute lymphoblastic leukemia (T-ALL) cells.
