diacylglycerol kinase

R 59-022 (DKGI-I) is a diacylglycerol kinase (DGK) inhibitor and a 5-HT Receptor antagonist that blocks filovirus internalization in host cells. R 59-022 activates protein kinase C (PKC), inhibits intestinal smooth muscle contractility, and enhances O2- production induced by 1-oleoyl-2-acetylglycerol.

R59949 is used as a Diacylglycerol kinase (DGK) inhibitor.

R 59-022 hydrochloride (DKGI-I hydrochloride) is a 5-HT Receptor antagonist that activates protein kinase C (PKC).R 59-022 hydrochloride is a DGK inhibitor (IC50:2.8 µM) that inhibits the phosphorylation of OAG to OAPA.R 59-022 enhances thrombin-induced triglyceride production in platelets and inhibits the production of phosphatidic acid in neutrophils. R 59-022 enhances thrombin-induced diglyceride production in platelets and inhibits phosphatidic acid production in neutrophils.

Dioctanoylglycol (ethane-1,2-diyl dioctanoate) is a diacylglycerol kinase inhibitor.

CU-3 is a potent and selective inhibitor of diacylglycerol kinase alpha (DGKalpha). CU-3 attenuates cancer cell proliferation and simultaneously enhances immune responses including anti-cancer immunity.

Protein kinase C (PKC ) is a calcium-independent, phospholipid- and diacylglycerol-dependent serine/threonine kinase involved in diverse signaling pathways, including those involved in neuronal signaling, cytoskeletal function, and inflammation.[1] PKC inhibitor peptide is a synthetic peptide corresponding to an amino acid sequence found in the amino terminal C2 domain of most mammalian forms of PKC .[2] It selectively and reversibly inhibits the translocation of PKC to intracellular membranes, blocking activation.[2] PKC inhibitor peptide is commonly used in cells to evaluate the role of PKC in various cellular responses.[3],[4],[5]

C8 D-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. It is cytotoxic to U937 cells (IC50 = 17 μM) and induces nuclear DNA fragmentation 5- to 6-fold more potently than C8 ceramide . C8 D-threo Ceramide is a substrate for E. coli diacylglycerol kinase. It activates ceramide-activated protein kinase (CAPK) in U937 cells. C8 D-threo Ceramide also enhances V. cholerae cytolysin pore formation in liposome lipid membranes, as measured by calcein release, with a 50% release dose (RD50) value of ~5 μg/ml.

1,2-Dioleoyl-rac-glycerol-13C3 is intended for use as an internal standard for the quantification of 1,2-dioleoyl-rac-glycerol by GC- or LC-MS. 1,2-dioleoyl-rac-glycerol is a diacylglycerol that contains oleic acid at the sn-1 and sn-2 positions. It effectively binds the C1 domain to activate conventional protein kinase C forms and serves as a substrate for diacylglycerol kinases and multisubstrate lipid kinase.1,2,3 |1. Yamaguchi, Y., Shirai, Y., Matsubara, T., et al. Phosphorylation and up-regulation of diacylglycerol kinase γ via its interaction with protein kinase Cγ. J. Biol. Chem. 281(42), 31627-31637 (2006).|2. Zhou, Q.Z., Raynor, R.L., Wood, M.G., Jr., et al. Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators. Biochemistry 27(19), 7361-7365 (1988).|3. Epand, R.M., Shulga, Y.V., Timmons, H.C., et al. Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Biochemistry 46(49), 14225-14231 (2007).

Phosphatidic acid is a phospholipid and an intermediate in glycerolipid biosynthesis. It is a transient intermediate in the synthesis of various phospholipid species that is synthesized de novo in cells via multiple routes, including the glycerol-3 phosphate and dihydroxyacetone phosphate pathways, enzymatic conversion of phosphatidylcholine by phospholipase D, and acetylation of lysophosphatidic acid by lysoPA-acyltransferase, among others. It has roles in shaping cellular membranes, cellular signaling, vesicle fission and fusion, as well as mitochondrial division and fusion. It stimulates respiratory burst in neutrophils independent of diacylglycerol and activates monoacylglycerol acyltransferase, phospholipase C (PLC), Ras, and phosphatidylinositol 4-phosphate (PIP4) kinase in several cell lines. Phosphatidic acids (egg) is a mixture of phosphatidic acids isolated from chicken egg with fatty acids of variable chain lengths.

JNJ-3790339 is an analogue of Ritanserin, a selective and potent diacylglycerol kinase (DGKα) inhibitor (IC50: 9.6 μM) that upregulates T-cell activation and induces toxic effects on malignant cells.

Cochlioquinone A is an inhibitor of diacylglycerol kinase (DGK) and diacylglycerol acyltransferase (DGAT). It has been shown to reduce the concentration of phosphatidic acid in T cell lymphoma and has also been shown to compete with macrophage inflammatory protein-1α for binding to human CCR5 chemokine receptors.

QNN33358 is an alkylacylglycerol acts as a protein kinase C (PKC) inhibitor and diacylglycerol (DAG) antagonist.

BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor that induces pERK activation, and it can be utilized in cancer research.

BMS-502 is a potent dual inhibitor of diacylglycerol kinase (DGK) α and ζ that induces immune responses in human and mouse T cells and blocks intracellular checkpoint signaling in T cells. BMS-502 stimulates immune responses in a dose-dependent manner and can be used to study immune-related diseases.

AMB639752 is a potent inhibitor of diacylglycerol kinase alpha (DGKα) that reinstates restimulation-induced cell death (RICD) in SAP-deficient lymphocytes through DGKα inhibition within intact cells. This compound is applicable in the research of X-linked lymphoproliferative disease 1 (XLP-1) [1].

DGKα-IN-6, a diacylglycerol kinase alpha (DGKα) inhibitor characterized by an inhibitory concentration (IC50) of 1.377 nM,holds promise for use in cancer research.

DGKα-IN-8 (Example 51), a potent diacylglycerol kinase alpha (DGKα) inhibitor, exhibits an IC50 of 22.491 nM and an EC50 of 0.256 nM. It is applicable in cancer research, particularly for solid tumors, and in studies of viral infections such as HIV and hepatitis B virus [1].

JH-131e-153, a diacylglycerol (DAG)-lactone, serves as a small molecule activator for the C1 domain of Munc13-1, exhibiting an activation hierarchy of WT>I590≈R592A≈W588A. This compound's C1 domain shares sequence and structure homology with protein kinase C (PKC), with an activation preference of PKCα>Munc13-1>PKCε. JH-131e-153 is implicated in the modulation of neuronal processes and holds potential for research in neurodegenerative diseases [1].

DGKζ-IN-3 is an inhibitor of diacylglycerol kinase zeta (DGK-ζ), employed in the treatment of both liquid and solid cancers, as well as other diseases regulated by DGK-ζ [1].

Protein kinase D (PKD), a serine threonine protein kinase activated by diacylglycerol downstream of PKC signaling, has three human isoforms that modulate cell proliferation, survival, invasion, and protein transport. CRT0066101 acts as an inhibitor of these three PKD isoforms, with IC50 values of 1, 2.5, and 2 nM for PKD1, PKD2, and PKD3, respectively. It demonstrates selectivity for PKD over a range of more than 90 protein kinases, including PKCα, PKBα, MEK, ERK, c-Raf, c-Src, and c-Abl. This specificity allows CRT0066101 to inhibit cell proliferation, induce apoptosis, and notably reduce the viability of pancreatic cancer cells both in vitro and in vivo.

Diacylglycerols (DAG) are generated through the hydrolysis of membrane phospholipids and function as lipid second messengers by activating protein kinase C (PKC) and modulating cell growth and apoptosis. Additionally, they act as precursors for DAG kinases in the synthesis of phosphatidic acid, a crucial lipid messenger. The compound 1-NBD-decanoyl-2-decanoyl-sn-glycerol incorporates a nitrobenzoxadiazole (NBD) fluorophore at the ω-end of its terminal decanoyl chain, using the structure of 1,2-didecanoyl-sn-glycerol as a model for diacylglycerol. This molecule is expected to exhibit excitation and emission peaks at roughly 470/541 nm, paralleling those of various NBD-labeled phospholipids. Fluorescently labeled lipids, such as this, are instrumental in exploring their interactions with proteins, their uptake by cells and liposomes, and in developing assays for lipid metabolism research.

ZKN14489, also known as 08:0 DG and 1,2-dioctanoyl-sn-glycerol, is a short-chain, cell-permeable diacylglycerol that serves as a lipid cofactor for activating protein kinase C.

1,3-Dioleoyl glycerol, a diacylglycerol with oleic acid at the sn-1 and sn-3 positions, activates protein kinase C (PKC) by approximately 30% at a concentration of 50 μM.

1-Palmitoyl-d9-2-palmitoyl-sn-glycerol serves as an internal standard for quantifying 1,2-dipalmitoyl-sn-glycerol using GC or LC-MS techniques. This diacylglycerol, featuring palmitic acid at both the sn-1 and sn-2 positions, stimulates protein kinase C (PKC) activity by 15% at a 25 μM concentration. Additionally, 1,2-dipalmitoyl-sn-glycerol encourages rapid growth in Frankia, a genus of Gram-positive bacteria.