Methyl Arachidonyl Fluorophosphonate

Names

[ Name ]:
Methyl Arachidonyl Fluorophosphonate

[Synonym ]:
Methyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraen-1-ylphosphonofluoridate
Methyl (5Z,8Z,11Z,14Z)-5,8,11,14-icosatetraen-1-ylphosphonofluoridate
Phosphonofluoridic acid, P-[(5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraen-1-yl]-, methyl ester
Methyl Arachidonyl Fluorophosphonate
MAPF,Phosphonofluoridic acid,methyl-5Z,8Z,11Z,14Z-eicosatetraenyl ester
Phosphonofluoridicacid
5Z,8Z,11Z,14Z-EICOSATETRAENYL-PHOSPHONOFLUORIDIC ACID,METHYL ESTER
MAPF
METHYLPHOSPHONOFLUORIDIC ACID 5,8,11,14-EICOSATETRAENYL ESTER
METHYL-5Z,8Z,11Z,14Z-EICOSATETRAENYL ESTER PHOSPHONOFLUORIDIC ACID METHYL ACETATE
MAFP

Biological Activity

[Description]:

MAFP (Methyl Arachidonyl Fluorophosphonate) is an selective, active-site directed and irreversible inhibitor of cPLA2 and iPLA2. MAFP is also a potent irreversible inhibitor of anandamide amidase.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

Research Areas >> Neurological Disease

Research Areas >> Cardiovascular Disease

Research Areas >> Metabolic Disease

[Target]

cPLA2, iPLA2[1], Anandamide amidase[2]

[In Vitro]

MAFP inhibits iPLA2, in a concentration-dependent manner with an IC50 of 5 μM after a 5 min preincubation at 40°C in P388D1 cells. cPLA, is a phospholipid hydrolase using the hydroxyl of serine-228 residue as its catalytic nucleophile[1]. MAFP is also an inhibitor of anandamide amidase and as a ligand for the CB1 cannabinoid receptor. MAFP demonstrates selectivity towards anandamide amidase for which it is approximately 3000 and 30000-fold more potent than it is towards chymotrypsin and trypsin, respectively. MAFP displaces [3H]CP-55940 binding to the CB1 cannabinoid receptor with an IC50 of 20 nM vs 40 nM for anandamide[2].

[Kinase Assay]

MAFP is dissolved and diluted in DMSO. To investigate the reversibility of iPLA 2 inhibition by MAFP, the P388D1 iPLA 2 is first concentrated approximately 10-fold using a Centricon-10 concentrator from Amicon. The concentrated iPLA 2 (20 μL) is then preincubated with either 80 μM MAFP in DMSO or DMSO alone (2 μL) for 5 min at 40°C. A 2 μL aliquot is removed and subsequently diluted 1500-fold into 3 mL of assay mixture containing 100 μM DPPC (200000 cpm per 50 μL assay mixture), 400 μM Triton X-100, 100 mM Hepes (pH 7.5), 5 mM EDTA, 1 mM DTT and 0.8 mM ATP. At the indicated time points, a 50 μL aliquot is removed and the remaining enzyme activity is quantified[1].

[Cell Assay]

Inhibition of anandamide amidase in cell culture is measured using approximately 1x106 Nl8TG2 intact neuroblastoma cells. Experimental cells are preincubated for 20 min in 1.5 mL medium, consisting of Fl2/DMEM with penicillin, streptomycin, gentamicin, 10% bovine calf serum, plus MAFP (1, 5, 10, 20 nM). Control cells contained no inhibitor. Arachidonoyl is then added and the incubation continued for I hr. The amount of [3H]anandamide in the cells is quantified by liquid scintillation counting of the silica scraped from the appropriate areas of the TLC plate identified by exposure to X-ray film[2].

[References]

[1]. Lio YC, et al. Irreversible inhibition of Ca(2+)-independent phospholipase A2 by methyl arachidonyl fluorophosphonate. Biochim Biophys Acta. 1996 Jul 12;1302(1):55-60.

[2]. Deutsch DG, et al. Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase. Biochem Pharmacol. 1997 Feb 7;53(3):255-60.

[Related Small Molecules]

U73122 | D609 | Darapladib | Quinacrine (dihydrochloride) | FIPI | Melittin | Varespladib | CAY10650 | AA26-9 | ML348 | Tanshinone I | ML 349 | 1-Monolinolein | Lp-PLA2 -IN-1 | SPK-601

Chemical & Physical Properties

[ Density]:
1.0±0.1 g/cm3

[ Boiling Point ]:
455.3±34.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₁H₃₆FO₂P

[ Molecular Weight ]:
370.482

[ Flash Point ]:
229.1±25.7 °C

[ Exact Mass ]:
370.243683

[ PSA ]:
36.11000

[ LogP ]:
7.44

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.474

[ Storage condition ]:
2-8℃

Safety Information

[ Hazard Codes ]:
F: Flammable;Xi: Irritant;

[ Risk Phrases ]:
R11

[ Safety Phrases ]:
16-26-29-33

[ RIDADR ]:
UN 1231 3/PG 2

Related Compounds

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