DIACYLGLYCEROL KINASE INHIBITOR I

Product NameDIACYLGLYCEROL KINASE INHIBITOR I
CAS93076-89-2
MFC27H26FN3OS
MW459.58
EINECS
MOL File93076-89-2.mol

Chemical Properties

Boiling point	619.8±65.0 °C(Predicted)
Density	1.26±0.1 g/cm3(Predicted)
storage temp.	-20°C
solubility	0.1 M HCl: slightly soluble
form	solid
pka	7.76±0.20(Predicted)
color	pale yellow
biological source	synthetic (organic)
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
InChI	1S/C27H26FN3OS/c1-19-24(26(32)31-17-18-33-27(31)29-19)13-16-30-14-11-22(12-15-30)25(20-5-3-2-4-6-20)21-7-9-23(28)10-8-21/h2-10,17-18H,11-16H2,1H3
InChIKey	MFVJXLPANKSLLD-UHFFFAOYSA-N
SMILES	Fc1ccc(cc1)C(=C3CCN(CC3)CCc4[c]([n]5c([s]cc5)nc4C)=O)c2ccccc2

Safety Information

Safety Statements	23-24/25
WGK Germany	3
Storage Class	11 - Combustible Solids

MSDS

Provider	Language
SigmaAldrich	English

Usage And Synthesis

Description

R-59022 (93076-89-2) is a diacylglycerol kinase (DAGK) inhibitor, nonselective for DAGK isotypes (IC50=2.8 μM in intact platelets).1 Induces autophagy and apoptosis in NG108-15 neuronal cells via an mTOR-independent mechanism.2 Prevents conjugated linoleic acid-mediated inflammatory signaling and insulin resistance in human adipocytes.3 Blocks filovirus internalization in host cells.4

Uses

R-59-022 acts as an inducer of apoptosis in glioblastoma cells and avoids apoptosis in non-cancerous cells. This selectivity makes this drug a highly effective anti-cancer agent. Diacylglycerol Kinase inhibitor.

Definition

ChEBI: 6-[2-[4-[(4-fluorophenyl)-phenylmethylidene]-1-piperidinyl]ethyl]-7-methyl-5-thiazolo[3,2-a]pyrimidinone is a diarylmethane.

Biological Activity

Diacylglycerol (DAG) kinase inhibitor (IC 50 = 2.8 μ M); increases protein kinase C activity. Potentiates thrombin-induced platelet aggregation and induces neutrophil chemotaxis. Inhibits U46619-induced contractions in mouse aorta and porcine coronary artery.

in vivo

R 59-022 (2 mg/kg, i.p., 12 days) significantly increases median survival in SCID mice implanted with U87 GBM cells^[6].

Animal Model:	SCID mice implanted with U87 GBM cells^[6]
Dosage:	10 mg/kg
Administration:	Intraperitoneal injection (i.p.)
Result:	Increased median survival and decreased tumor volume.

IC 50

PKC; serotonin; diacylglycerol kinase: 2.8 μM (IC₅₀)

References

[1] D C DE CHAFFOY DE COURCELLES H V B P Roevens. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet.[J]. The Journal of Biological Chemistry, 1985, 260 29: 15762-15770.
[2] TSUYOSHI TAKITA. Diacylglycerol kinase inhibitor R59022-induced autophagy and apoptosis in the neuronal cell line NG108-15[J]. Archives of biochemistry and biophysics, 2011, 509 2: Pages 197-201. DOI:10.1016/j.abb.2011.02.007
[3] KRISTINA MARTINEZ. Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes.[J]. Journal of Lipid Research, 2013, 54 3: 662-670. DOI:10.1194/jlr.m031211
[4] CORINA M STEWART. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells.[J]. Viruses-Basel, 2019, 11 3. DOI:10.3390/v11030206

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