R59949

[Description]:

R59949 is a pan diacylglycerol kinase (DGK) inhibitor with an IC50 of 300 nM. R59949 strongly inhibits the activity of type I DGK α and γ and moderately attenuates the activity of type II DGK θ and κ. R59949 activates protein kinase C (PKC) by enhancing the levels of the endogenous ligand diacyl glycerol[1][2][3].

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PKC

Research Areas >> Cancer

Signaling Pathways >> TGF-beta/Smad >> PKC

[In Vitro]

In the presence of R59949, vasopressin- as well as collagen-induced release reaction and aggregation was strongly increased, independently of the formation of arachidonate metabolites[1]. In THP‐1 monocytes, R59949 attenuates CCL2‐evoked Ca2+ signalling with a half‐maximal concentration of 8.6 μM[2]. R59949 inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells[4].

[References]

[1]. de Chaffoy de Courcelles D, et al. The role of endogenously formed diacylglycerol in the propagation and termination of platelet activation. A biochemical and functional analysis using the novel diacylglycerol kinase inhibitor, R 59 949. J Biol Chem. 1989;264(6):3274-3285.

[2]. Day P, et al. Inhibitors of DAG metabolism suppress CCR2 signalling in human monocytes. Br J Pharmacol. 2019;176(15):2736-2749.

[3]. Meinhardt G, et al. Effect of novel modulators of protein kinase C activity upon chemotherapy-induced differentiation and apoptosis in myeloid leukemic cells. Anticancer Drugs. 2002;13(7):725-733.

[4]. Shimomura T, et al. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(2):207-214.

[ Density]:
1.36g/cm3

[ Boiling Point ]:
637.1ºC at 760mmHg

[ Molecular Formula ]:
C₂₈H₂₅F₂N₃OS

[ Molecular Weight ]:
489.57900

[ Flash Point ]:
339.1ºC

[ Exact Mass ]:
489.16900

[ PSA ]:
73.12000

[ LogP ]:
5.87310

[ Vapour Pressure ]:
3.94E-16mmHg at 25°C

[ Index of Refraction ]:
1.688

[ Storage condition ]:
-20°C

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
NONH for all modes of transport

Diacylglycerol kinase α promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src.

Oncotarget 5(20) , 9710-26, (2014)

Diacylglycerol kinase (DGK)α converts diacylglycerol to phosphatidic acid. This lipid kinase sustains survival, migration and invasion of tumor cells, with no effect over untransformed cells, suggesti...

Insulin action on polyunsaturated phosphatidic acid formation in rat brain: an "in vitro" model with synaptic endings from cerebral cortex and hippocampus.

Neurochem. Res. 34(7) , 1236-48, (2009)

The highly efficient formation of phosphatidic acid from exogenous 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) in rat brain synaptic nerve endings (synaptosomes) from cerebral cortex and hippocampus i...

Effect of novel modulators of protein kinase C activity upon chemotherapy-induced differentiation and apoptosis in myeloid leukemic cells.

Anticancer Drugs 13(7) , 725-33, (2002)

Modulation of protein kinase C (PKC) activity has been demonstrated to either prevent or enhance drug-induced apoptosis in various tissue types. We tested four novel modulators of PKC activity in comp...

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