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A small molecule inhibitor of diacylglycerol kinase (DGK) with IC50 of 2.8 uM, inhibits the phosphorylation of OAG to OAPA with IC50 of 3.8 uM in intact platelets; concomitantly stimulates PKC activity, selectively suppresses U46619-induced enhancement of mouse portal vein contraction under high glucose conditions; also induces caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacks toxicity in noncancerous cells.
R-59949 (R59949;R 59949) is a small molecule inhibitor of diacylglycerol kinase (DGK) with IC50 of 0.01-10 uM in isolated platelet membranes and in intact platelets; markedly increases PKC activity in platelets stimulated with vasopressin, produces partial inhibition of formation of phosphatidic acid in human platelets challenged with thrombin, DC8 or OAG; also induces caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacks toxicity in noncancerous cells.
CU-3 (DGKα inhibitor CU-3) is a novel potent, selective diacylglycerol kinase α (DGKα) inhibitor with IC50 of 0.6 uM, targets the catalytic region, but not the regulatory region; CU-3 competitively reduces the affinity of DGKα for ATP, but not diacylglycerol or phosphatidylserine, displays selectivity over other nine isozymes (IC50>7 uM); induces apoptosis in HepG2 hepatocellular carcinoma and HeLa cervical cancer cells while simultaneously enhancing the interleukin-2 production of Jurkat T cells.
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