Methoxy arachidonyl fluorophosphonate explained

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]

See also

• DIFP – diisopropyl fluorophosphate, a related inhibitor
• IDFP – isopropyl dodecylfluorophosphonate, another related inhibitor with selectivity for FAAH and MAGL
• Activity-based probes

Notes and References

1. Hoover HS, Blankman JL, Niessen S, Cravatt BF . Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling . Bioorg. Med. Chem. Lett. . 18. 22. 5838–41. July 2008 . 18657971 . 10.1016/j.bmcl.2008.06.091 . 2634297.
2. Deutsch DG, Omeir R, Arreaza G, Salehani D, Prestwich GD, Huang Z, Howlett A . Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase . Biochem. Pharmacol. . 53 . 3 . 255–60 . 1997 . 9065728 . 10.1016/s0006-2952(96)00830-1.
3. Savinainen JR, Saario SM, Niemi R, Järvinen T, Laitinen JT . 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 . 2003 . 14623770 . 1574161 . 10.1038/sj.bjp.0705577 .
4. 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.