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Monoacylglycerol lipase

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Target not currently curated in GtoImmuPdb

Target id: 1399

Nomenclature: Monoacylglycerol lipase

Abbreviated Name: MAGL

Family: S33: Prolyl aminopeptidase, 2-Acylglycerol ester turnover, Hydrolases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 303 3q21.3 MGLL monoglyceride lipase
Mouse - 303 6 D1 Mgll monoglyceride lipase
Rat - 303 4q34 Mgll monoglyceride lipase
Previous and Unofficial Names Click here for help
HU-K5 | MGL | MAGL | monoacylglycerol lipase
Database Links Click here for help
Specialist databases
MEROPS S33.980 (Hs)
Other databases
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human monoacylglycerol lipase in complex with compound 4f
PDB Id:  7L50
Ligand:  compound 4f [PMID: 34328319]
Resolution:  2.3Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 3.1.1.23
Endogenous substrates (Human)
2-oleoyl glycerol = 2-arachidonoylglycerol >> anandamide  [5]

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
JJKK 048 Small molecule or natural product Hs Inhibition 9.3 pIC50 1
pIC50 9.3 [1]
JNJ-42226314 Small molecule or natural product Hs Inhibition 8.9 pIC50 10
pIC50 8.9 (IC50 1.13x10-9 M) [10]
Description: In vitro potency of JNJ-42226314 to inhibit human MAGL using an in vitro [3H]2-OG cleavage activity assay.
ABD-1970 Small molecule or natural product Click here for species-specific activity table Rn Inhibition 8.5 pIC50 4
pIC50 8.5 (IC50 3x10-9 M) [4]
Description: MAGL in rat brain cortex
KML29 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 2
pIC50 8.5 [2]
JZL184 Small molecule or natural product Hs Irreversible inhibition 8.4 pIC50 2
pIC50 8.4 (IC50 3.9x10-9 M) [2]
JZL195 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 7
pIC50 8.4 (IC50 4x10-9 M) [7]
Description: in vitro assay
compound 4f [PMID: 34328319] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.2 pIC50 6
pIC50 8.2 (IC50 6.2x10-9 M) [6]
MJN110 Small molecule or natural product Hs Inhibition 8.0 pIC50 8
pIC50 8.0 (IC50 9.1x10-9 M) [8]
ABX-1431 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Irreversible inhibition 7.8 pIC50 3
pIC50 7.8 (IC50 1.4x10-8 M) [3]
compound 36 [PMID: 32429662] Small molecule or natural product Hs Inhibition 7.8 pIC50 11
pIC50 7.8 (IC50 1.5x10-8 M) [11]
ABD-1970 Small molecule or natural product Click here for species-specific activity table Mm Inhibition 7.8 pIC50 4
pIC50 7.8 (IC50 1.5x10-8 M) [4]
Description: MAGL in mouse brain
ABD-1970 Small molecule or natural product Hs Inhibition 7.7 pIC50 4
pIC50 7.7 (IC50 1.8x10-8 M) [4]
Description: hMAGL from PC3 cell lysate
ABX-1431 Small molecule or natural product Mm Irreversible inhibition 7.6 pIC50 3
pIC50 7.6 (IC50 2.7x10-8 M) [3]
SA-57 Small molecule or natural product Click here for species-specific activity table Mm Inhibition 6.4 pIC50 9
pIC50 6.4 (IC50 4.1x10-7 M) [9]
SA-57 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.8 pIC50 9
pIC50 5.8 (IC50 1.4x10-6 M) [9]
View species-specific inhibitor tables
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0006954 inflammatory response TAS
GO:0050727 regulation of inflammatory response ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response ISS

References

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1. Aaltonen N, Savinainen JR, Ribas CR, Rönkkö J, Kuusisto A, Korhonen J, Navia-Paldanius D, Häyrinen J, Takabe P, Käsnänen H et al.. (2013) Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase. Chem Biol, 20 (3): 379-90. [PMID:23521796]

2. Chang JW, Niphakis MJ, Lum KM, Cognetta 3rd AB, Wang C, Matthews ML, Niessen S, Buczynski MW, Parsons LH, Cravatt BF. (2012) Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem Biol, 19 (5): 579-88. [PMID:22542104]

3. Cisar JS, Weber OD, Clapper JR, Blankman JL, Henry CL, Simon GM, Alexander JP, Jones TK, Ezekowitz RAB, O'Neill GP et al.. (2018) Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders. J Med Chem, 61 (20): 9062-9084. [PMID:30067909]

4. Clapper JR, Henry CL, Niphakis MJ, Knize AM, Coppola AR, Simon GM, Ngo N, Herbst RA, Herbst DM, Reed AW et al.. (2018) Monoacylglycerol Lipase Inhibition in Human and Rodent Systems Supports Clinical Evaluation of Endocannabinoid Modulators. J Pharmacol Exp Ther, 367 (3): 494-508. [PMID:30305428]

5. Ghafouri N, Tiger G, Razdan RK, Mahadevan A, Pertwee RG, Martin BR, Fowler CJ. (2004) Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol. Br J Pharmacol, 143 (6): 774-84. [PMID:15492019]

6. Ikeda S, Sugiyama H, Tokuhara H, Murakami M, Nakamura M, Oguro Y, Aida J, Morishita N, Sogabe S, Dougan DR et al.. (2021) Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl Moiety. J Med Chem, 64 (15): 11014-11044. [PMID:34328319]

7. Long JZ, Nomura DK, Vann RE, Walentiny DM, Booker L, Jin X, Burston JJ, Sim-Selley LJ, Lichtman AH, Wiley JL et al.. (2009) Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo. Proc Natl Acad Sci USA, 106 (48): 20270-5. [PMID:19918051]

8. Niphakis MJ, Cognetta 3rd AB, Chang JW, Buczynski MW, Parsons LH, Byrne F, Burston JJ, Chapman V, Cravatt BF. (2013) Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors. ACS Chem Neurosci, 4 (9): 1322-32. [PMID:23731016]

9. Niphakis MJ, Johnson DS, Ballard TE, Stiff C, Cravatt BF. (2012) O-hydroxyacetamide carbamates as a highly potent and selective class of endocannabinoid hydrolase inhibitors. ACS Chem Neurosci, 3 (5): 418-26. [PMID:22860211]

10. Wyatt RM, Fraser I, Welty N, Lord B, Wennerholm M, Sutton S, Ameriks MK, Dugovic C, Yun S, White A et al.. (2020) Pharmacologic Characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a Reversible, Selective, and Potent Monoacylglycerol Lipase Inhibitor. J Pharmacol Exp Ther, 372 (3): 339-353. [PMID:31818916]

11. Zhi Z, Zhang W, Yao J, Shang Y, Hao Q, Liu Z, Ren Y, Li J, Zhang G, Wang J. (2020) Discovery of Aryl Formyl Piperidine Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase Inhibitors. J Med Chem, 63 (11): 5783-5796. [PMID:32429662]

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