From Wikipedia, the free encyclopedia
Methoxy arachidonyl fluorophosphonate
Names
Preferred IUPAC name
Methyl [(5Z ,8Z ,11Z ,14Z )-icosa-5,8,11,14-tetraen-1-yl]phosphonofluoridate
Other names
MAFP
Identifiers
ChEMBL
ChemSpider
EC Number
InChI=1S/C21H36FO2P/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-25(22,23)24-2/h7-8,10-11,13-14,16-17H,3-6,9,12,15,18-21H2,1-2H3/b8-7-,11-10-,14-13-,17-16-
Y Key: KWKZCGMJGHHOKJ-ZKWNWVNESA-N
Y
FP(=O)(OC)CCCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
Properties
C21 H36 FO2 P
Molar mass
370.5
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Methoxy arachidonyl fluorophosphonate , commonly referred as MAFP , is an irreversible active site-directed
enzyme inhibitor that inhibits nearly all
serine hydrolases and
serine proteases .
[1] It inhibits
phospholipase A2 and
fatty acid amide hydrolase with special potency, displaying
IC50 values in the low-nanomolar range. In addition, it binds to the
CB1 receptor in rat brain membrane preparations (
IC50 = 20 nM),
[2] but does not appear to
agonize or
antagonize the receptor,
[3] though some related derivatives do show cannabinoid-like properties.
[4]
DIFP – diisopropyl fluorophosphate, a related inhibitor
IDFP – isopropyl dodecylfluorophosphonate, another related inhibitor with selectivity for FAAH and MAGL
Activity-based probes
^ Hoover HS, Blankman JL, Niessen S, Cravatt BF (July 2008).
"Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling" . Bioorg. Med. Chem. Lett . 18 (22): 5838–41.
doi :
10.1016/j.bmcl.2008.06.091 .
PMC
2634297 .
PMID
18657971 .
^ Deutsch DG, Omeir R, Arreaza G, Salehani D, Prestwich GD, Huang Z, Howlett A (1997). "Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase". Biochem. Pharmacol . 53 (3): 255–60.
doi :
10.1016/s0006-2952(96)00830-1 .
PMID
9065728 .
^ Savinainen JR, Saario SM, Niemi R, Järvinen T, Laitinen JT (2003).
"An optimized approach to study endocannabinoid signaling: evidence against constitutive activity of rat brain adenosine A1 and cannabinoid CB1 receptors" . Br. J. Pharmacol . 140 (8): 1451–9.
doi :
10.1038/sj.bjp.0705577 .
PMC
1574161 .
PMID
14623770 .
^ Martin BR, Beletskaya I, Patrick G, Jefferson R, Winckler R, Deutsch DG, Di Marzo V, Dasse O, Mahadevan A, Razdan RK. Cannabinoid properties of methylfluorophosphonate analogs. J Pharmacol Exp Ther . 2000 Sep;294(3):1209-18.
PMID
10945879
Receptor (
ligands )
DP (D2 ) Tooltip Prostaglandin D2 receptor
DP1 Tooltip Prostaglandin D2 receptor 1
DP2 Tooltip Prostaglandin D2 receptor 2
EP (E2 ) Tooltip Prostaglandin E2 receptor
EP1 Tooltip Prostaglandin EP1 receptor
EP2 Tooltip Prostaglandin EP2 receptor
EP3 Tooltip Prostaglandin EP3 receptor
EP4 Tooltip Prostaglandin EP4 receptor Unsorted
FP (F2α ) Tooltip Prostaglandin F receptor
IP (I2 ) Tooltip Prostacyclin receptor
TP (TXA2 ) Tooltip Thromboxane receptor Unsorted
Enzyme (
inhibitors )
COX (
PTGS )
PGD2 S Tooltip Prostaglandin D synthase
PGES Tooltip Prostaglandin E synthase
PGFS Tooltip Prostaglandin F synthase
PGI2 S Tooltip Prostacyclin synthase
TXAS Tooltip Thromboxane A synthase
Others
Receptor (
ligands )
BLT Tooltip Leukotriene B4 receptor
BLT1 Tooltip Leukotriene B4 receptor 1
BLT2 Tooltip Leukotriene B4 receptor 2
CysLT Tooltip Cysteinyl leukotriene receptor
CysLT1 Tooltip Cysteinyl leukotriene receptor 1
CysLT2 Tooltip Cysteinyl leukotriene receptor 2
CysLTE Tooltip Cysteinyl leukotriene receptor E
Enzyme (
inhibitors )
5-LOX Tooltip Arachidonate 5-lipoxygenase
12-LOX Tooltip Arachidonate 12-lipoxygenase
15-LOX Tooltip Arachidonate 15-lipoxygenase
LTA4 H Tooltip Leukotriene A4 hydrolase
LTB4 H Tooltip Leukotriene B4 ω-hydroxylase
LTC4 S Tooltip Leukotriene C4 synthase
LTC4 H Tooltip Leukotriene C4 hydrolase
LTD4 Tooltip Leukotriene D4 hydrolase
Others
Receptor (
ligands )
CB1 Tooltip Cannabinoid receptor type 1
Agonists(abridged,
full list ) Inverse agonists Antagonists
CB2 Tooltip Cannabinoid receptor type 2
Agonists
2-AG
2-AGE (noladin ether)
3,3'-Diindolylmethane
4-O-Methylhonokiol
α-Amyrin · β-Amyrin
A-796,260
A-834,735
A-836,339
AM-1172
AM-1221
AM-1235
AM-1241
AM-2232
Anandamide
AZ-11713908
Cannabinol
Caryophyllene
CB-13
CBS-0550
CP 55,940
GW-405,833 (L-768,242)
GW-842,166X
HU-308
JTE 7-31
JWH-007
JWH-015
JWH-018
JWH-73
JWH-133
L-759,633
L-759,656
Lenabasum (anabasum)
Magnolol
MDA-19
Nabitan
NADA
Olorinab (APD-371)
PF-03550096
S-444,823
SER-601
Serinolamide A
UR-144
Tedalinab
THC (dronabinol)
THCV
Tetrahydromagnolol
Virodhamine
Antagonists
NAGly (
GPR18 )
GPR55
GPR119
Transporter (
modulators )
eCBTs Tooltip Endocannabinoid transporter
Enzyme (
modulators )
Others
Others:
2-PG (directly potentiates activity of 2-AG at CB1 receptor)
ARN-272 (FAAH-like anandamide transporter inhibitor)