Arachidonyl trifluoromethyl ketone

Names

[ Name ]:
Arachidonyl trifluoromethyl ketone

[Synonym ]:
Arachidonic acid trifluoromethyl ketone
AACOCF3
Arachidonyl trifluoromethyl ketone
UNII:00XIW1CR0F
Arachidonic acid trifluoromethylketone
MFCD00236427
6,9,12,15-Heneicosatetraen-2-one, 1,1,1-trifluoro-, (6Z,9Z,12Z,15Z)-
(6Z,9Z,12Z,15Z)-1,1,1-Trifluoro-6,9,12,15-henicosatetraen-2-one
Arach-CF3
Arachidonyltrifluoromethane
(6Z,9Z,12Z,15Z)-1,1,1-Trifluorohenicosa-6,9,12,15-tetraen-2-one

Biological Activity

[Description]:

AACOCF3 (Arachidonyl trifluoromethyl ketone) is a cell-permeant trifluoromethyl ketone analog of arachidonic acid. AACOCF3 is a potent and selective slow binding inhibitor of the 85-kDa cytosolic phospholipase A2 (cPLA2). AACOCF3 blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. AACOCF3 inhibits glucose-induced insulin secretion from isolated rat islets. AACOCF3 has the potential for the research of cardiovascular disease[1][2][3].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

[In Vitro]

AACOCF3 inhibits the release of arachidonic acid from calcium ionophore-challenged U937 cells (IC50= 8 μM, 2 x 106 cells ml-1) and from platelets (IC50= 2 μM, 4 x 107 cells ml-1)[1]. AACOCF3 (10 μM) suppresses phosphate-induced calcification and osteogenic/chondrogenic signaling in HAoSMCs. AACOCF3 significantly inhibits both basal and Pi-induced release of arachidonic acid, the product of PLA2 activity[2].

[In Vivo]

AACOCF3 (10 mg/kg; gavage; 5 days a week; ApoE–/– mice (6-week-old males) were fed a high-cholesterol diet) significantly reduces type III collagen plaque expression but had no significant influence on total collagen accumulation[3].

[References]

[1]. Riendeau D, et al. Arachidonyl trifluoromethyl ketone, a potent inhibitor of 85-kDa phospholipase A2, blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. J Biol Chem. 1994;269(22):15619-15624.

[2]. Schanstra JP, et al. Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment. JCI Insight. 2019;4(10):e125638. Published 2019 May 16.

[3]. Loweth AC, et al. A specific inhibitor of cytosolic phospholipase A2 activity, AACOCF3, inhibits glucose-induced insulin secretion from isolated rat islets. Biochem Biophys Res Commun. 1996;218(2):423-427.

Chemical & Physical Properties

[ Density]:
1.0±0.1 g/cm3

[ Boiling Point ]:
421.7±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₁H₃₁F₃O

[ Molecular Weight ]:
356.465

[ Flash Point ]:
288.7±20.2 °C

[ Exact Mass ]:
356.232697

[ PSA ]:
17.07000

[ LogP ]:
7.78

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.463

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;half-mask respirator (US);multi-purpose combination respirator cartridge (US)

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Articles

Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway.

J. Neuroinflammation 12 , 199, (2015)

Oxidative stress and inflammation are important factors contributing to the pathophysiology of numerous neurological disorders, including Alzheimer's disease, Parkinson's disease, acute stroke, and in...

Cytoplasmic phospholipase A₂ modulation of adolescent rat ethanol-induced protein kinase C translocation and behavior.

Neurochem. Res. 40 , 1023-31, (2015)

Ethanol consumption typically begins during adolescence, a developmental period which exhibits many age-dependent differences in ethanol behavioral sensitivity. Protein kinase C (PKC) activity is larg...

Inhibition of cytosolic phospholipase A(2) alpha protects against focal ischemic brain damage in mice.

Brain Res. 1471 , 129-37, (2012)

It is postulated that inhibition of cytosolic phospholipase A(2) alpha (cPLA(2)α) can reduce severity of stroke injury. This is supported by the finding that cPLA(2)α-deficient mice are partially prot...