MGLL

Summary

MGLL (monoglyceride lipase, HGNC:17038) is a protein-coding gene on chromosome 3q21.3, encoding Monoglyceride lipase (Q99685). Converts monoacylglycerides to free fatty acids and glycerol.

This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 11343 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 47 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17038
Approved symbol	MGLL
Name	monoglyceride lipase
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	HU-K5, MGL, MAGL
Ensembl gene	ENSG00000074416
Ensembl biotype	protein_coding
OMIM	609699
Entrez	11343

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000265052, ENST00000398101, ENST00000398104, ENST00000453507, ENST00000465597, ENST00000476654, ENST00000476682, ENST00000479967, ENST00000487473, ENST00000493611, ENST00000494830, ENST00000496306, ENST00000648300, ENST00000864851, ENST00000864852, ENST00000864853, ENST00000864854, ENST00000864855, ENST00000864856, ENST00000959996, ENST00000959997

RefSeq mRNA: 10 — MANE Select: NM_007283 NM_001003794, NM_001256585, NM_001388312, NM_001388313, NM_001388314, NM_001388315, NM_001388316, NM_001388317, NM_001388318, NM_007283

CCDS: CCDS43148, CCDS46902, CCDS58852

Canonical transcript exons

ENST00000265052 — 8 exons

Exon	Start	End
ENSE00000968265	127710576	127710665
ENSE00001881088	127689066	127692323
ENSE00003468769	127694975	127695190
ENSE00003471817	127721053	127721163
ENSE00003573885	127722430	127722566
ENSE00003619631	127821694	127821838
ENSE00003785570	127781789	127781895
ENSE00003917324	127822309	127822515

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.5422 / max 594.0582, expressed in 1621 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44410	28.1948	1472
44402	5.4620	1214
44411	3.6176	1269
44405	0.7376	381
44403	0.6287	359
44412	0.5636	313
44404	0.4936	227
44415	0.3884	191
44406	0.3874	198
44408	0.3530	178

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	98.85	gold quality
ileal mucosa	UBERON:0000331	98.42	gold quality
mucosa of transverse colon	UBERON:0004991	97.98	gold quality
lower esophagus mucosa	UBERON:0035834	97.89	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.78	gold quality
adipose tissue	UBERON:0001013	97.70	gold quality
apex of heart	UBERON:0002098	97.41	gold quality
connective tissue	UBERON:0002384	97.35	gold quality
right frontal lobe	UBERON:0002810	97.35	gold quality
epithelium of esophagus	UBERON:0001976	97.27	gold quality
endothelial cell	CL:0000115	97.17	gold quality
esophagus squamous epithelium	UBERON:0006920	97.15	gold quality
olfactory bulb	UBERON:0002264	97.01	gold quality
pericardium	UBERON:0002407	96.95	gold quality
rectum	UBERON:0001052	96.81	gold quality
pharyngeal mucosa	UBERON:0000355	96.77	gold quality
lower lobe of lung	UBERON:0008949	96.73	gold quality
prefrontal cortex	UBERON:0000451	96.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.68	gold quality
cingulate cortex	UBERON:0003027	96.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.62	gold quality
anterior cingulate cortex	UBERON:0009835	96.60	gold quality
mouth mucosa	UBERON:0003729	96.59	gold quality
oral cavity	UBERON:0000167	96.56	gold quality
vena cava	UBERON:0004087	96.56	gold quality
minor salivary gland	UBERON:0001830	96.55	gold quality
frontal cortex	UBERON:0001870	96.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.54	gold quality
frontal lobe	UBERON:0016525	96.53	gold quality
cerebellar hemisphere	UBERON:0002245	96.48	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	927.42
E-GEOD-75688	yes	873.96
E-MTAB-6075	yes	173.58
E-HCAD-5	yes	46.64
E-CURD-112	yes	34.73
E-MTAB-8142	yes	25.24
E-GEOD-125970	yes	22.82
E-HCAD-6	yes	18.84
E-MTAB-9067	yes	12.16
E-CURD-114	yes	11.70
E-GEOD-84465	yes	11.66
E-MTAB-8498	yes	8.66
E-MTAB-10596	no	224.52
E-MTAB-10137	no	4.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PRDM5

miRNA regulators (miRDB)

100 targeting MGLL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538

Literature-anchored findings (GeneRIF, showing 40)

• not associated with susceptibility to alcoholism in a Japanese population. (PMID:17621164)
• full proteomic characterization of hMGL was carried out, which showed (1) an absence of intramolecular disulfide bridges in the functional, recombinant enzyme and (2) the post-translational removal of the enzyme’s N-terminal methionine (PMID:18452279)
• Identification of amino acids critical to the catalytic activity (PMID:18721756)
• Gene Ontology analysis indicated a significant alteration of oxygen transport (increased hemoglobin gene expression) and lipid metabolism [including monoglyceride lipase and low density lipoprotein receptor-related protein 5 (LRP5) gene]. (PMID:19233690)
• An apolar helix covering the active site also gives structural insight into the amphitropic character of MAGL, and likely explains how MAGL interacts with membranes to recruit its substrate. (PMID:19957260)
• MGL shares the classic fold of the alpha/beta hydrolase family but depicts an unusually large hydrophobic occluded tunnel with a highly flexible lid at its entry and the catalytic triad buried at its end. (PMID:19962385)
• Study shows that monoacylglycerol lipase (MAGL) is highly expressed in aggressive cancer cells and primary tumors; it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and tumor growth. (PMID:20079333)
• Identification of an active site hydrogen bond network in human monoacylglycerol lipase. (PMID:20464001)
• Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid in the brain and is believed to be hydrolyzed primarily by serine hydrolase monoacylglycerol lipase (MAGL) in a transgenic mouse model with targeted disruption of MAGL. (PMID:20855465)
• One interval in the FAAH promoter and three intervals in the MGLL gene were associated with high BMI. (PMID:21118518)
• Data present a high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase. (PMID:21308848)
• High MAGL is associated with colorectal cancer. (PMID:21543155)
• MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. (PMID:21802006)
• results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth (PMID:22349814)
• No association was found between our inflammatory bowel disease cohort and the candidate single nucleotide polymorphisms for MGL (CD/HC: P=0.37 and UC/HC: P=0.25). (PMID:22664939)
• MGL expression declines after peaking in infancy. (PMID:22827915)
• Data indicate that N,N-dimethyl-5-(4-phenoxyphenyl)-2H-tetrazole-2-carboxamide inhibited monoacylglycerol lipase (MAGL) with IC50 0.028 muM. (PMID:23455058)
• MGL interaction with a phospholipid membrane bilayer induces regional changes in the enzyme’s conformation that favor its recruiting lipophilic substrate from membrane stores to the active site resulting in enhanced MGL catalytic activity. (PMID:23553709)
• Mutation of Cys242 was also found to impair inhibition of monoacylglycerol lipase. (PMID:24368842)
• In obese humans, FAAH or MGL activity in adipocytes is not affected by diabetes, dyslipidaemia or other markers of metabolic dysfunction. (PMID:24593280)
• In subcutaneous adipose tissue, DAGL-a mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diets had no influence. (PMID:24616451)
• role of monoacylglycerol lipase (MAGL) in the cancer progress (PMID:24633487)
• Molecular dynamics and nudged elastic band simulations were used to explore the conformational transition pathway of the helix alpha4 of human monoacylglycerol lipase. (PMID:25078047)
• Our findings establish that MAGL promotes metastases in nasopharyngeal carcinoma (PMID:25120746)
• The study identified monoacylglycerol lipase as a YAP transcriptional target and an inhibitor of anchorage-dependent cell growth. (PMID:25636199)
• Monoacylglycerol lipase sulfenylation might act as an intrinsic neuroprotective mechanism by potentiating 2-AG signaling at CB1 receptors. (PMID:26000748)
• The data highlight specific inter-residue interactions within hMGL (PMID:26555264)
• there was evidence that MGLL rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the endocannabinoid system and addiction (PMID:26595473)
• the presence and differential distribution of fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in relation to CB1 during the maturation of human oocytes, was investigated. (PMID:26948343)
• This study unravels a novel mechanism of SND1 function and identifies MGLL as a unique tumor suppressor for HCC. MGLL might function as a homeostatic regulator of Akt restraining its activation. (PMID:26997225)
• MGLL may have a role in progression of gastrointestinal stromal tumors (PMID:27366945)
• RNA interference, specific pharmacological inhibitor JZL-184 and gene knock-in of MAGL were utilized to investigate the effects of MAGL on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, and invasion. MAGL played important roles in both proliferation and invasion of HCC cells. (PMID:27767105)
• the upregulation of MAGL in hepatocellular carcinoma cells promoted cell growth and invasiveness abilities, and mediated epithelial-mesenchymal transition (PMID:27884159)
• we clarify the key role of Phe159 and Ile179, two conserved residues within the lid domain, in regulating substrate specificity in MAGL. We conclude by proposing that other structurally related lipases may share this lid-domain-mediated mechanism for substrate specificity. (PMID:28088576)
• This review summarizes the basics of monoglyceride metabolism and provides an overview on the therapeutic potential of MGL. [Review] (PMID:28213089)
• Using a multimethod approach, the authors show that the dynamically relevant Trp-289 and Leu-232 residues serve as communication hubs within an allosteric protein network that controls signal propagation to the active site, and thus, regulates active-inactive interconversion of human MGL. (PMID:29379013)
• Study utilizing colorectal cancer patients tissue samples, mouse tumor cell lines and xenograft models identify MGLL as a switch for CB2/TLR4-dependent macrophage activation and provide potential targets for cancer therapy. (PMID:29968710)
• Low mRNA expression and activity of monoacylglycerol lipase in human SH-SY5Y neuroblastoma cells (PMID:30978461)
• overexpression of MAGL inhibits the proliferation of MHCC97H hepatocellular carcinoma cells in vivo, and its mechanism may be associated to the release of inflammatory factors from tumor-associated macrophages (PMID:31357777)
• Brain structural changes in cannabis dependence: association with MAGL. (PMID:31695165)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mgll	ENSDARG00000036820
mus_musculus	Mgll	ENSMUSG00000033174
rattus_norvegicus	Mgll	ENSRNOG00000014508

Protein

Protein identifiers

Monoglyceride lipase — Q99685 (reviewed: Q99685)

Alternative names: HU-K5, Lysophospholipase homolog, Lysophospholipase-like, Monoacylglycerol lipase

All UniProt accessions (6): Q99685, A0A0C4DFN3, A0A3B3ITT3, C9JAM4, H7C4E0, H7C5K5

UniProt curated annotations — full annotation on UniProt →

Function. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Tissue specificity. Detected in adipose tissue, lung, liver, kidney, brain and heart.

Pathway. Glycerolipid metabolism; triacylglycerol degradation.

Miscellaneous. Short-term inhibition causes analgesia, while long-term inhibition causes tolerance to endocannabinoids acting on brain cannabinoid receptor CNR1, and a reduction in brain cannabinoid receptor CNR1 activity.

Similarity. Belongs to the AB hydrolase superfamily. Monoacylglycerol lipase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99685-1	1	yes
Q99685-2	2

RefSeq proteins (10): NP_001003794, NP_001243514, NP_001375241, NP_001375242, NP_001375243, NP_001375244, NP_001375245, NP_001375246, NP_001375247, NP_009214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR022742	ABHD17C-like	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR051044	MAG_DAG_Lipase	Family

Pfam: PF12146

Enzyme classification (BRENDA):

• EC 3.1.1.23 — acylglycerol lipase (BRENDA: 16 organisms, 181 substrates, 293 inhibitors, 72 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

25 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-ARACHIDONOYLGLYCEROL	0.0097–0.122	12
4-METHYLUMBELLIFERYL BUTYRATE	0.084–0.162	11
MONOACYLGLYCEROL	0.15–0.3	8
2-OLEOYLGLYCEROL	—	7
2-(15-DEOXY-DELTA12,14-PROSTAGLANDIN J2)-GLYCERO	0.01–0.016	5
1-MONOOLEOYLGLYCEROL	0.083–0.51	3
LYSOPHOSPHATIDYLETHANOLAMINE	0.22–0.28	3
1(3)-MONOOLEOYLGLYCEROL	0.27	1
1-DECANOYL-RAC-GLYCEROL	0.02	1
1-MONOLAUROYLGLYCEROL	0.14	1
1-MONOMYRISTOYLGLYCEROL	0.12	1
2-MONOMYRISTOYLGLYCEROL	0.2	1
2-MONOOLEOYLGLYCEROL	0.059	1
4-NITROPHENYL ACETATE	0.2	1
7-HYDROXYCOUMARINYL ARACHIDONATE	0.0098	1

Catalyzed reactions (Rhea), 12 shown:

• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• a 1-acylglycerol + H2O = glycerol + a fatty acid + H(+) (RHEA:34019)
• 1-octadecanoylglycerol + H2O = octadecanoate + glycerol + H(+) (RHEA:38363)
• 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38487)
• 2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38491)
• 1-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+) (RHEA:39959)
• 2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+) (RHEA:39963)
• 1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+) (RHEA:44312)
• 1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+) (RHEA:44316)
• 1-decanoylglycerol + H2O = decanoate + glycerol + H(+) (RHEA:44320)
• 1-octanoylglycerol + H2O = octanoate + glycerol + H(+) (RHEA:44328)
• a 2-acylglycerol + H2O = glycerol + a fatty acid + H(+) (RHEA:44688)

UniProt features (39 total): helix 13, strand 11, mutagenesis site 4, active site 3, turn 2, modified residue 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
9F8D	X-RAY DIFFRACTION	1.14
7ZPG	X-RAY DIFFRACTION	1.16
3PE6	X-RAY DIFFRACTION	1.35
5ZUN	X-RAY DIFFRACTION	1.35
9F8B	X-RAY DIFFRACTION	1.4
9G4M	X-RAY DIFFRACTION	1.41
8RVF	X-RAY DIFFRACTION	1.43
9FY5	X-RAY DIFFRACTION	1.43
9I3Y	X-RAY DIFFRACTION	1.45
9I5J	X-RAY DIFFRACTION	1.48
9I56	X-RAY DIFFRACTION	1.49
9I9C	X-RAY DIFFRACTION	1.49
8PTC	X-RAY DIFFRACTION	1.51
9F8C	X-RAY DIFFRACTION	1.52
9Q8D	X-RAY DIFFRACTION	1.54
8AQF	X-RAY DIFFRACTION	1.55
8PTQ	X-RAY DIFFRACTION	1.55
9F8A	X-RAY DIFFRACTION	1.56
7PRM	X-RAY DIFFRACTION	1.65
8PTR	X-RAY DIFFRACTION	1.73
6BQ0	X-RAY DIFFRACTION	2
3JW8	X-RAY DIFFRACTION	2.1
3HJU	X-RAY DIFFRACTION	2.2
7L4T	X-RAY DIFFRACTION	2.2
7L4W	X-RAY DIFFRACTION	2.2
7L4U	X-RAY DIFFRACTION	2.25
6AX1	X-RAY DIFFRACTION	2.26
7L50	X-RAY DIFFRACTION	2.3
4UUQ	X-RAY DIFFRACTION	2.36
3JWE	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99685-F1	94.36	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 122 (nucleophile); 239 (charge relay system); 269 (charge relay system)

Post-translational modifications (2): 10, 58

Mutagenesis-validated functional residues (4):

Position	Phenotype
208	does not affect ability to hydrolyze 1- or 2-monoacylglycerol.
242	reduced 1-monoacylglycerol lipase activity.
194	does not affect ability to hydrolyze 1- or 2-monoacylglycerol.
201	does not affect ability to hydrolyze 1- or 2-monoacylglycerol.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-1482883	Acyl chain remodeling of DAG and TAG
R-HSA-163560	Triglyceride catabolism
R-HSA-426048	Arachidonate production from DAG
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-109582	Hemostasis
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-162582	Signal Transduction
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-416476	G alpha (q) signalling events
R-HSA-556833	Metabolism of lipids
R-HSA-74160	Gene expression (Transcription)
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-8979227	Triglyceride metabolism
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 395 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, MODULE_52, HNF3ALPHA_Q6, LU_IL4_SIGNALING, GOBP_INFLAMMATORY_RESPONSE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, CMYB_01, MODULE_128, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, AP2_Q3, FOXO1_01, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, BEIER_GLIOMA_STEM_CELL_DN

GO Biological Process (16): lipid metabolic process (GO:0006629), fatty acid biosynthetic process (GO:0006633), inflammatory response (GO:0006954), regulation of signal transduction (GO:0009966), arachidonate metabolic process (GO:0019369), triglyceride catabolic process (GO:0019433), acylglycerol catabolic process (GO:0046464), regulation of inflammatory response (GO:0050727), regulation of sensory perception of pain (GO:0051930), monoacylglycerol catabolic process (GO:0052651), regulation of endocannabinoid signaling pathway (GO:2000124), fatty acid metabolic process (GO:0006631), lipid catabolic process (GO:0016042), regulation of axon extension (GO:0030516), long-term synaptic depression (GO:0060292), regulation of retrograde trans-synaptic signaling by endocanabinoid (GO:0099178)

GO Molecular Function (6): phosphatidylcholine lysophospholipase A1 activity (GO:0004622), protein homodimerization activity (GO:0042803), monoacylglycerol lipase activity (GO:0047372), protein binding (GO:0005515), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (11): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasm (GO:0005737), axon (GO:0030424), varicosity (GO:0043196), synapse (GO:0045202), parallel fiber to Purkinje cell synapse (GO:0098688), presynapse (GO:0098793), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Metabolism of lipids	2
Glycerophospholipid biosynthesis	1
Triglyceride metabolism	1
Effects of PIP2 hydrolysis	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Phospholipid metabolism	1
Gene expression (Transcription)	1
Signal Transduction	1
Signaling by GPCR	1
GPCR downstream signalling	1
Metabolism	1
Hemostasis	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
acylglycerol catabolic process	2
lipid metabolic process	2
primary metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
defense response	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
triglyceride metabolic process	1
acylglycerol metabolic process	1
neutral lipid catabolic process	1
glycerolipid catabolic process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
sensory perception of pain	1
regulation of sensory perception	1
monoacylglycerol metabolic process	1
regulation of G protein-coupled receptor signaling pathway	1
endocannabinoid signaling pathway	1
monocarboxylic acid metabolic process	1
catabolic process	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
regulation of synaptic plasticity	1
negative regulation of synaptic transmission	1
retrograde trans-synaptic signaling by endocannabinoid	1
regulation of trans-synaptic signaling	1
lysophospholipase A1 activity	1
identical protein binding	1
protein dimerization activity	1

Protein interactions and networks

STRING

2716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGLL	FAAH	O00519	973
MGLL	NCEH1	Q6PIU2	960
MGLL	CNR1	P21554	941
MGLL	LIPE	Q05469	925
MGLL	NAPEPLD	Q6IQ20	920
MGLL	ABHD6	Q9BV23	895
MGLL	DAGLA	Q9Y4D2	885
MGLL	ABHD12	Q8N2K0	832
MGLL	DAGLB	Q8NCG7	830
MGLL	CES1	P23141	807
MGLL	PNPLA2	Q96AD5	801
MGLL	GPR55	Q9Y2T6	777
MGLL	ABHD5	Q8WTS1	748
MGLL	TRPV1	Q8NER1	729
MGLL	ABHD4	Q8TB40	721

IntAct

16 interactions, top by confidence:

A	B	Type	Score
MGLL	HPCAL1	psi-mi:“MI:0915”(physical association)	0.640
MGLL	HPCAL1	psi-mi:“MI:0914”(association)	0.640
SPATA46	TYW5	psi-mi:“MI:0914”(association)	0.530
MGLL	ADRB2	psi-mi:“MI:0915”(physical association)	0.510
MGLL	HTR4	psi-mi:“MI:0915”(physical association)	0.370
MGLL	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
USE1	NBAS	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
	MGLL	psi-mi:“MI:0915”(physical association)	0.000
mdtI	MGLL	psi-mi:“MI:0915”(physical association)	0.000
MGLL	CHGB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): MGLL (Affinity Capture-MS), MGLL (Affinity Capture-MS), HPCAL1 (Affinity Capture-MS), MGLL (Co-crystal Structure), MGLL (Affinity Capture-MS), MGLL (Affinity Capture-MS), HPCAL1 (Affinity Capture-MS), MGLL (Two-hybrid), MGLL (Affinity Capture-RNA), MGLL (Two-hybrid), CHGB (Two-hybrid), AQP6 (Two-hybrid), COQ9 (Two-hybrid), CD79A (Two-hybrid), PEX12 (Two-hybrid)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, A6NNS2, B0BN93, B0BNF8, O22718, O35331, O35678, O75911, O77769, O80526, O88876, O95154, P11172, P14755, P15904, P84169, Q06136, Q15738, Q1RMJ5, Q28DS0, Q2KIJ5, Q2QNG7, Q2QZ86, Q3SZM9, Q3T067, Q3ZBE9, Q5E964, Q5I0K3, Q5PPL3, Q5R514, Q5R5C9, Q5RDZ2, Q6AY30, Q6UWP2, Q811X6, Q86WA6, Q8JGT5, Q8K183

Diamond homologs: A0A7H0DN16, A0QNZ7, O07427, O35678, P18379, P18380, P21084, P68464, P68465, Q8R431, Q99685, C6L862, O64252, Q55EQ3, Q83WC8, A1KRU9, A9W3H8, B1ZB18, B7KWT4, C5B0U6, C7CM33, E6MWF8, L0TC47, P59337, Q5F641, Q5NZF6, Q7MPY0, Q7NPW5, Q8K4F5, Q8NFV4, Q98C03, Q9JSN0, Q9K197, O34705, O94305, P07000, P59588, B4F753, Q4R766, Q99LR1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SND1	“down-regulates quantity by destabilization”	MGLL	binding
MGLL	down-regulates	Proliferation

Disease & clinical

Clinical variants and AI predictions

ClinVar

47 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3767 predictions. Top by Δscore:

Variant	Effect	Δscore
3:127694970:CTCA:C	donor_loss	1.0000
3:127694971:TCAC:T	donor_loss	1.0000
3:127694972:CACCT:C	donor_loss	1.0000
3:127694973:A:AC	donor_gain	1.0000
3:127694973:AC:A	donor_gain	1.0000
3:127694974:C:CC	donor_gain	1.0000
3:127694974:C:G	donor_loss	1.0000
3:127694974:CC:C	donor_gain	1.0000
3:127710570:TCTCA:T	donor_loss	1.0000
3:127710571:CTCA:C	donor_loss	1.0000
3:127710572:TCAC:T	donor_loss	1.0000
3:127710573:CAC:C	donor_loss	1.0000
3:127710574:A:C	donor_loss	1.0000
3:127710575:C:G	donor_loss	1.0000
3:127710575:CCT:C	donor_gain	1.0000
3:127710664:ACC:A	acceptor_loss	1.0000
3:127710666:CT:C	acceptor_loss	1.0000
3:127721159:CCTCC:C	acceptor_gain	1.0000
3:127721160:CTCC:C	acceptor_gain	1.0000
3:127721160:CTCCC:C	acceptor_gain	1.0000
3:127721161:TCCCT:T	acceptor_gain	1.0000
3:127721162:CC:C	acceptor_gain	1.0000
3:127721163:CC:C	acceptor_gain	1.0000
3:127722564:CAA:C	acceptor_gain	1.0000
3:127722567:C:CC	acceptor_gain	1.0000
3:127781782:CACT:C	donor_loss	1.0000
3:127781783:ACTC:A	donor_loss	1.0000
3:127781784:CTCA:C	donor_loss	1.0000
3:127781785:TCA:T	donor_loss	1.0000
3:127781786:CA:C	donor_loss	1.0000

AlphaMissense

2039 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:127722435:A:G	S122P	0.998
3:127692305:G:C	H269D	0.996
3:127695123:A:G	L213P	0.996
3:127722557:C:T	G81E	0.996
3:127692303:A:C	H269Q	0.995
3:127692303:A:T	H269Q	0.995
3:127695046:C:G	D239H	0.995
3:127695115:C:G	A216P	0.995
3:127721096:G:C	S146W	0.995
3:127695055:C:G	G236R	0.994
3:127721163:C:G	G124R	0.994
3:127721163:C:T	G124R	0.994
3:127722434:G:T	S122Y	0.994
3:127722557:C:A	G81V	0.994
3:127695035:A:C	C242W	0.993
3:127695045:T:A	D239V	0.993
3:127721162:C:T	G124E	0.993
3:127722550:G:C	S83R	0.993
3:127722550:G:T	S83R	0.993
3:127722552:T:G	S83R	0.993
3:127722563:C:T	G79D	0.993
3:127781794:T:A	D76V	0.993
3:127781794:T:G	D76A	0.993
3:127692305:G:T	H269N	0.992
3:127721087:A:T	V149D	0.992
3:127721162:C:A	G124V	0.992
3:127781795:C:G	D76H	0.992
3:127781876:G:C	H49D	0.992
3:127692243:C:A	W289C	0.991
3:127692243:C:G	W289C	0.991

dbSNP variants (sampled 300 via entrez): RS1000016657 (3:127743182 G>A), RS1000025461 (3:127779686 G>A), RS1000056884 (3:127755729 T>C), RS1000072855 (3:127818972 C>G), RS1000085311 (3:127741051 G>T), RS1000107902 (3:127767316 C>G,T), RS1000108277 (3:127703171 T>C), RS1000141135 (3:127779375 A>T), RS1000165494 (3:127748446 G>A), RS1000182429 (3:127709909 A>G), RS1000197814 (3:127722689 C>G), RS1000217739 (3:127705179 T>C), RS1000250751 (3:127784808 T>C), RS1000310664 (3:127734856 A>C), RS1000338913 (3:127791040 T>A)

Disease associations

OMIM: gene MIM:609699 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002337_53	Amyotrophic lateral sclerosis (sporadic)	6.000000e-09
GCST009179_4	Pars triangularis volume	3.000000e-07
GCST010002_438	Refractive error	9.000000e-21
GCST010151_11	Carotid intima media thickness x smoking interaction	4.000000e-06
GCST012490_609	Femur bone mineral density x serum urate levels interaction	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4191 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 118,452 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL120563	THIRAM	2	79,340
CHEMBL3945728	ELCUBRAGISTAT	2	84
CHEMBL184238	URB-597	1	417

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2-Acylglycerol ester turnover

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
LEI-515	Inhibition	9.3	pIC50
JJKK 048	Inhibition	9.3	pIC50
JNJ-42226314	Inhibition	8.95	pIC50
KML29	Inhibition	8.5	pIC50
JZL195	Inhibition	8.4	pIC50
MAGLi 432	Inhibition	8.38	pIC50
compound 4f [PMID: 34328319]	Inhibition	8.21	pIC50
JZL184	Inhibition	8.1	pIC50
MJN110	Inhibition	8.04	pIC50
ABX-1431	Irreversible inhibition	7.85	pIC50
compound 36 [PMID: 32429662]	Inhibition	7.82	pIC50
ABD-1970	Inhibition	7.74	pIC50
pristimerin	Inhibition	7.03	pIC50
CAY10499	Inhibition	6.84	pIC50
SA-57	Inhibition	5.85	pIC50

Binding affinities (BindingDB)

177 measured of 312 human assays (355 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro- 2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2- methylbenzo[d]oxazol-6-yl)methanone;	IC50	0.64 nM	US-11597728: Monoacylglycerol lipase modulators
(3-(1H-1,2,4-Triazol-1-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2- methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol- 10-yl)methanone;	IC50	1.5 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-(2-Chloro-3-methoxyphenyl)((5R,9S)-3-(3-fluorophenyl)- 2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	1.87 nM	US-11597728: Monoacylglycerol lipase modulators
N-pyridazin-3-yl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]piperidine-1-carboxamide	IC50	1.9 nM	US-12378231: Small molecules as monoacylglycerol lipase (MAGL) inhibitors, compositions and use thereof
racemic-((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6- yl)methanone;	IC50	2.3 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-ethyl-1- phenyl-1H-1,2,4-triazol-3-yl)methanone;	IC50	2.82 nM	US-11597728: Monoacylglycerol lipase modulators
(1-Methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)((5R,9S)-2-methyl-3- (3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	7 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-(2-Chloro-3-methoxyphenyl)((5R,9S)-3-(4-fluorophenyl)- 2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	7.85 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-1- phenyl-1H-1,2,4-triazol-3-yl)methanone;	IC50	9.52 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-phenyl- 1H-1,2,4-triazol-3-yl)methanone;	IC50	10.4 nM	US-11597728: Monoacylglycerol lipase modulators
(2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(4-fluorophenyl)-2- methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol- 10-yl)methanone;	IC50	11.7 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-2-Cyclopropyl-3-(3-fluorophenyl)-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6- yl)methanone;	IC50	11.8 nM	US-11597728: Monoacylglycerol lipase modulators
((5R,9S)-3-(4-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H- 5,9-epiminocycloocta[c]pyrazol-10-yl)(1-methyl-1H-pyrazolo[3,4- b]pyridin-3-yl)methanone;	IC50	18.7 nM	US-11597728: Monoacylglycerol lipase modulators
(6-Methoxypyrazolo[1,5-a]pyridin-3-yl)((5R,9S)-2-methyl-3- (3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	18.9 nM	US-11597728: Monoacylglycerol lipase modulators
[(1S,8R)-5-(4-fluorophenyl)-4-methyl-3,4,12-triazatricyclo[6.3.1.02,6]dodeca-2,5-dien-12-yl]-quinolin-6-ylmethanone	IC50	22.6 nM	US-11597728: Monoacylglycerol lipase modulators
((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro- 2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxypyridin-3- yl)methanone;	IC50	36.5 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[2-(3-methylpyrrolidin-1-yl)-1,3-benzoxazole-6-carbonyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	52 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
2-[4-[2-[3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]-1,3-benzoxazole-6-carbonyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	53 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
1-[4-[N-(1,3-benzodioxol-5-yl)-4-fluoroanilino]piperidine-1-carbonyl]benzotriazole-5-carbonitrile	IC50	55 nM	US-12378231: Small molecules as monoacylglycerol lipase (MAGL) inhibitors, compositions and use thereof
((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro- 2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxybenzofuran- 2-yl)methanone;	IC50	63.7 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxy- 1-methyl-1H-pyrazol-4-yl)methanone;	IC50	65.1 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[4-[(1S,2S)-2-phenylcyclopropyl]benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	70 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
racemic-(5-Cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-4- yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	74.7 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-(5-Cyclopropyl-1H-pyrazol-4-yl)((5R,9S)-3-(3,5- difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	76 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[4-(2-azabicyclo[2.2.1]heptan-2-yl)benzoyl]piperazin-1-yl]-4aH-quinazolin-4-one	IC50	81 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(4- fluorophenyl)-5-methyl-1H-1,2,4-triazol-3-yl)methanone;	IC50	81.1 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[4-(2,5-dimethylpyrrolidin-1-yl)benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	84 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
2-[4-[2-(3-fluoro-3-methylpyrrolidin-1-yl)-1,3-benzoxazole-6-carbonyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	90 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
1-[4-[bis(4-fluorophenyl)methyl]piperazine-1-carbonyl]benzotriazole-5-carbonitrile	IC50	100 nM	US-12378231: Small molecules as monoacylglycerol lipase (MAGL) inhibitors, compositions and use thereof
((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro- 2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-fluoropyridin-4- yl)methanone;	IC50	101 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-(5-Cyclopropyl-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol- 4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	117 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[2-(3-methoxypyrrolidin-1-yl)-1,3-benzoxazole-6-carbonyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	121 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
(5-Aminopyridin-2-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl- 4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10- yl)methanone;	IC50	130 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-(3-Cyclopropyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4- yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	139 nM	US-11597728: Monoacylglycerol lipase modulators
racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9- hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-ethyl-5- (trifluoromethyl)-1H-pyrazol-3-yl)methanone;	IC50	179 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[4-[3-(methoxymethyl)pyrrolidin-1-yl]benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	206 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
racemic-(5-Cyclopropyl-1-phenyl-1H-pyrazol-4-yl)((5R,9S)-3-(3,5- difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9- epiminocycloocta[c]pyrazol-10-yl)methanone;	IC50	265 nM	US-11597728: Monoacylglycerol lipase modulators
2-[4-[4-(2-phenylpyrrolidin-1-yl)benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	270 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
2-[4-[2-(3-hydroxy-3-methylpyrrolidin-1-yl)-1,3-benzoxazole-6-carbonyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	297 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
2-[4-[4-[(1R,2S)-2-phenylcyclopropyl]benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	340 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
2-[4-[4-[3-(1-hydroxyethyl)pyrrolidin-1-yl]benzoyl]piperazin-1-yl]-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-4-one	IC50	440 nM	US-11390610: Piperazine derivatives as MAGL inhibitors
1,1,1,3,3,3-hexafluoropropan-2-yl 2-[[2-(4-acetylcyclohexyl)-4-(trifluoromethyl)phenyl]methyl]-2,8-diazaspiro[4.5]decane-8-carboxylate	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
1-[5-fluoro-2-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-2,8-diazaspiro[4.5]decan-2-yl]methyl]phenyl]piperidine-4-carboxylic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
3-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-1,8-diazaspiro[4.5]decan-1-yl]methyl]-5-methylbenzoic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
1-[[2-chloro-5-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-2,8-diazaspiro[4.5]decan-2-yl]methyl]phenyl]methyl]piperidine-4-carboxylic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
5-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-2,8-diazaspiro[4.5]decan-2-yl]methyl]-2-(trifluoromethyl)benzoic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
4-[5-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-2,8-diazaspiro[4.5]decan-2-yl]methyl]-2-(trifluoromethyl)phenyl]-2-methylmorpholine-2-carboxylic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
2-chloro-5-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-1,8-diazaspiro[4.5]decan-1-yl]methyl]benzoic acid	IC50	550 nM	US-10030020: Spirocycle compounds and methods of making and using same
2-[2-fluoro-6-[[4-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)piperazin-1-yl]methyl]-3-methylphenoxy]acetic acid	IC50	550 nM	US-10093635: MAGL inhibitors
1-[4-[bis(4H-1,3-benzodioxin-6-yl)methoxy]piperidine-1-carbonyl]benzotriazole-5-carbonitrile	IC50	550 nM	US-12378231: Small molecules as monoacylglycerol lipase (MAGL) inhibitors, compositions and use thereof

ChEMBL bioactivities

2378 potent at pChembl≥5 of 2523 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.85	IC50	0.014	nM	CHEMBL5785193
10.72	IC50	0.019	nM	CHEMBL5283351
10.68	IC50	0.021	nM	CHEMBL5569248
10.62	IC50	0.024	nM	CHEMBL5074982
10.57	IC50	0.027	nM	CHEMBL5832941
10.52	IC50	0.03	nM	CHEMBL4749516
10.52	IC50	0.03	nM	CHEMBL5618354
10.47	IC50	0.034	nM	CHEMBL5282368
10.41	IC50	0.039	nM	CHEMBL5892322
10.40	IC50	0.04	nM	CHEMBL4759880
10.40	IC50	0.04	nM	CHEMBL4785835
10.40	IC50	0.04	nM	CHEMBL5080928
10.40	IC50	0.04	nM	CHEMBL5618586
10.39	IC50	0.041	nM	CHEMBL5996643
10.32	IC50	0.048	nM	CHEMBL5793684
10.30	IC50	0.05	nM	CHEMBL5575673
10.30	IC50	0.05	nM	CHEMBL5569248
10.22	IC50	0.06	nM	CHEMBL5620312
10.22	IC50	0.06	nM	CHEMBL5618723
10.22	IC50	0.06	nM	CHEMBL5620200
10.15	IC50	0.07	nM	CHEMBL4745872
10.12	IC50	0.075	nM	CHEMBL5280083
10.10	IC50	0.08	nM	CHEMBL5619084
10.09	IC50	0.082	nM	CHEMBL5941658
10.07	IC50	0.086	nM	CHEMBL3787346
10.07	IC50	0.086	nM	CHEMBL5901923
10.06	IC50	0.088	nM	CHEMBL5747079
10.03	IC50	0.094	nM	CHEMBL6030416
10.02	IC50	0.095	nM	CHEMBL5751521
10.01	IC50	0.097	nM	CHEMBL5783701
10.00	IC50	0.1	nM	CHEMBL4756662
10.00	IC50	0.1	nM	CHEMBL4749293
10.00	IC50	0.1	nM	CHEMBL5992406
10.00	IC50	0.1	nM	CHEMBL5977282
10.00	IC50	0.1	nM	CHEMBL6025412
9.96	IC50	0.11	nM	CHEMBL5766234
9.96	IC50	0.11	nM	CHEMBL5809976
9.96	IC50	0.11	nM	CHEMBL6043445
9.85	IC50	0.14	nM	CHEMBL5989783
9.77	IC50	0.17	nM	CHEMBL6017690
9.74	IC50	0.18	nM	CHEMBL4097203
9.74	IC50	0.18	nM	CHEMBL4059676
9.74	IC50	0.18	nM	CHEMBL6067709
9.74	IC50	0.18	nM	CHEMBL5938868
9.70	IC50	0.2	nM	CHEMBL5089721
9.70	IC50	0.198	nM	CHEMBL3785379
9.70	IC50	0.2	nM	CHEMBL5766195
9.68	IC50	0.21	nM	CHEMBL5268216
9.68	IC50	0.21	nM	CHEMBL6029674
9.64	IC50	0.23	nM	CHEMBL5806570

PubChem BioAssay actives

1038 with measured affinity, of 2109 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4aR,8aS)-6-[3-[4-[2-(trifluoromethyl)phenyl]phenyl]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	<0.0001	uM
(4aR,8aS)-6-[3-[4-(2,4-dichlorophenyl)phenyl]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	<0.0001	uM
(4aR,8aS)-6-[3-[4-[2-(trifluoromethoxy)phenyl]phenyl]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	<0.0001	uM
2-[6-[4-(1-methylcyclopropyl)phenyl]-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1956446: Inhibition of MGL activity in human HeLa cells assessed as reduction in cleaved [1,3-3H glycerol] level using [glycerol-1,3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	<0.0001	uM
2-[6-(4-tert-butylphenyl)-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1956446: Inhibition of MGL activity in human HeLa cells assessed as reduction in cleaved [1,3-3H glycerol] level using [glycerol-1,3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	<0.0001	uM
N-methyl-6-oxo-N-[3-(4-propan-2-ylphenyl)cyclobutyl]-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	<0.0001	uM
2-[6-(3-tert-butylphenyl)-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1815773: Inhibition of human MGL expressed in human HeLa cells assessed as amount of cleaved glycerol measured after 1 hrs by flow through assay	ic50	<0.0001	uM
2-[6-[3-(1-methylcyclopropyl)phenyl]-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1815773: Inhibition of human MGL expressed in human HeLa cells assessed as amount of cleaved glycerol measured after 1 hrs by flow through assay	ic50	<0.0001	uM
(3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[1-(benzotriazole-1-carbonyl)piperidin-4-yl]-3-(4-fluorophenyl)azetidin-2-one	2099302: Inhibition of human MAGL	ic50	<0.0001	uM
[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	<0.0001	uM
[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	<0.0001	uM
(3S,4R)-4-(1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)-1-[1-(1,2,4-triazole-1-carbonyl)piperidin-4-yl]azetidin-2-one	2099302: Inhibition of human MAGL	ic50	0.0001	uM
(4aR,8aS)-6-[3-[4-(2,2-dimethylpropyl)phenyl]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	0.0001	uM
2-[4-[1-[(4aR,8aS)-3-oxo-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazine-6-carbonyl]azetidin-3-yl]phenyl]-3-chlorobenzonitrile	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	0.0001	uM
(4aR,8aS)-6-[4-[(R)-(4-methylphenyl)-phenylmethyl]piperidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1694504: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry	ic50	0.0001	uM
2-[6-(3-chloro-4-methylphenyl)-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1956446: Inhibition of MGL activity in human HeLa cells assessed as reduction in cleaved [1,3-3H glycerol] level using [glycerol-1,3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0001	uM
[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	0.0001	uM
[6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	0.0001	uM
[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	0.0001	uM
[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone	2128392: Inhibition of human MAGL using 2-arachidonoylglycerol as substrate assessed as reduction in substrate hydrolysis by measuring arachidonic acid formation preincubated for 15 mins followed by substrate addition and measured after 30 mins by triple quadrupole mass spectrometric analysis	ic50	0.0001	uM
(3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[1-(benzotriazole-1-carbonyl)piperidin-4-yl]-3-(3-fluorophenyl)azetidin-2-one	2099302: Inhibition of human MAGL	ic50	0.0001	uM
(3R,4S)-4-(1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)-1-[1-(1,2,4-triazole-1-carbonyl)piperidin-4-yl]azetidin-2-one	2099302: Inhibition of human MAGL	ic50	0.0002	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-(1-phenylpyrazol-3-yl)azetidine-1-carboxylate	1477446: Inhibition of human recombinant MAGL using 7-HCA as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0002	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-[1-(3,4-difluorophenyl)pyrazol-3-yl]azetidine-1-carboxylate	1477446: Inhibition of human recombinant MAGL using 7-HCA as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0002	uM
2-[6-(4-propan-2-ylphenyl)-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1956446: Inhibition of MGL activity in human HeLa cells assessed as reduction in cleaved [1,3-3H glycerol] level using [glycerol-1,3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0002	uM
N-[3-(4-tert-butylphenyl)cyclobutyl]-N-methyl-6-oxo-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0002	uM
(3R,4S)-3,4-diphenyl-1-[1-(1,2,4-triazole-1-carbonyl)piperidin-4-yl]azetidin-2-one	2099302: Inhibition of human MAGL	ic50	0.0002	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-(1,5-diphenylpyrazol-3-yl)azetidine-1-carboxylate	1477446: Inhibition of human recombinant MAGL using 7-HCA as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0003	uM
2-[1-(4-cyclopropyl-2-methylphenyl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1815773: Inhibition of human MGL expressed in human HeLa cells assessed as amount of cleaved glycerol measured after 1 hrs by flow through assay	ic50	0.0003	uM
N-[3-(4-cyclopropyl-3-methylphenyl)cyclobutyl]-N-methyl-6-oxo-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0003	uM
N-methyl-N-[3-[4-(1-methylcyclopropyl)phenyl]cyclobutyl]-6-oxo-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0003	uM
1-[(R)-[2-chloro-4-[(2S,3S)-4-(3-chlorophenyl)-2,3-dimethylpiperazine-1-carbonyl]phenyl]sulfinyl]-3,3-difluoropentan-2-one	2085900: Inhibition of human MAGL overexpressing HEK293T using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured every 5 mins for 60 mins in presence of ATP by fluorescence based analysis	ic50	0.0003	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-(3-phenyl-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate	1477446: Inhibition of human recombinant MAGL using 7-HCA as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0004	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-(1-benzylpyrazol-3-yl)azetidine-1-carboxylate	1477446: Inhibition of human recombinant MAGL using 7-HCA as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0004	uM
(4aR,8aS)-6-[3-[(4-chloro-2-phenoxyphenyl)methoxy]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1759752: Inhibition of recombinant MAGL (unknown origin) using 4-Nitrophenlyacetate as substrate incubated for 15 mins followed by substrate addition and measured after 5 mins	ic50	0.0004	uM
N-[3-(3-tert-butyl-4-fluorophenyl)cyclobutyl]-N-methyl-6-oxo-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0004	uM
[4-[bis(1,3-benzodioxol-5-yl)methyl]piperidin-1-yl]-(1,2,4-triazol-1-yl)methanone	1167641: Inhibition of human recombinant MAGL expressed in HEK293 cells using 2-AG as substrate	ic50	0.0004	uM
[4-[(3-phenoxyphenyl)methyl]piperazin-1-yl]-(1,2,4-triazol-1-yl)methanone	1167641: Inhibition of human recombinant MAGL expressed in HEK293 cells using 2-AG as substrate	ic50	0.0005	uM
1-[2-chloro-4-[(2S,3S)-4-(3-chlorophenyl)-2,3-dimethylpiperazine-1-carbonyl]phenyl]sulfinyl-3,3-difluoropentan-2-one	2085900: Inhibition of human MAGL overexpressing HEK293T using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured every 5 mins for 60 mins in presence of ATP by fluorescence based analysis	ic50	0.0005	uM
N-[3-(3-cyclopropyl-5-methylphenyl)cyclobutyl]-N-methyl-6-oxo-7-oxa-5-azaspiro[3.4]octane-2-carboxamide	1813838: Inhibition of human MAGL expressed in HeLa cells using [glycerol-1, 3-3H]-oleoyl glycerol as substrate incubated for 1 hr	ic50	0.0005	uM
ethyl 2-[4-[3-methyl-4-(3-methylphenyl)piperazine-1-carbonyl]-2-nitrophenyl]sulfinylacetate	2085900: Inhibition of human MAGL overexpressing HEK293T using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured every 5 mins for 60 mins in presence of ATP by fluorescence based analysis	ic50	0.0005	uM
4-[[2-chloro-3-[3-(3,5-difluorophenyl)-2,7-dimethyl-5,7-dihydro-4H-pyrazolo[3,4-c]pyridine-6-carbonyl]-5-fluorophenoxy]methyl]pyrrolidin-2-one	2005712: Inhibition of MAGL (unknown origin) using 2-arachidonoylglycerol as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 30 mins by mass spectrometer analysis	ic50	0.0005	uM
(4-benzhydrylpiperazin-1-yl)-(benzotriazol-1-yl)methanone	693811: Inhibition of human MAGL assessed as [3H]-2-OG hydrolysis preincubated for 30 mins before [3H]-2-OG addition measured after 10 mins by liquid scintillation counting	ic50	0.0005	uM
1-[3-(2-chlorophenyl)phenyl]-4-[4-(1,3-thiazole-2-carbonyl)piperazin-1-yl]pyrrolidin-2-one	1387472: Inhibition of His-tagged human MAGL expressed in Escherichia coli BL21(DE3) assessed as reduction in arachidonic acid production from 2-arachidonoylglycerol pre-incubated for 60 mins by mass spectrometry	ic50	0.0006	uM
[4-[bis(1,3-benzodioxol-5-yl)methylidene]piperidin-1-yl]-(1,2,4-triazol-1-yl)methanone	1363896: Inhibition of human MAGL	ic50	0.0006	uM
1-[2-chloro-4-[(2S,3S)-4-(4-chloro-2-pyridinyl)-2,3-dimethylpiperazine-1-carbonyl]phenyl]sulfinyl-3,3-difluoropentan-2-one	2085900: Inhibition of human MAGL overexpressing HEK293T using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured every 5 mins for 60 mins in presence of ATP by fluorescence based analysis	ic50	0.0006	uM
[4-[bis(1,3-benzodioxol-5-yl)-hydroxymethyl]piperidin-1-yl]-(1,2,4-triazol-1-yl)methanone	1167641: Inhibition of human recombinant MAGL expressed in HEK293 cells using 2-AG as substrate	ic50	0.0007	uM
(4aR,8aS)-6-[3-[2-[2-bromo-4-(trifluoromethyl)phenyl]ethyl]azetidine-1-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one	1759752: Inhibition of recombinant MAGL (unknown origin) using 4-Nitrophenlyacetate as substrate incubated for 15 mins followed by substrate addition and measured after 5 mins	ic50	0.0007	uM
2-[(1R,5S)-6-(4-tert-butylphenyl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one	1815773: Inhibition of human MGL expressed in human HeLa cells assessed as amount of cleaved glycerol measured after 1 hrs by flow through assay	ic50	0.0007	uM
7-[4-(5-phenyl-2-pyridinyl)piperazine-1-carbonyl]-1H-quinolin-2-one	2102335: Inhibition of recombinant human MAGL preincubated for 10 mins followed by substrate addition and measured every 10 sec for 10 mins	ic50	0.0007	uM

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	4
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
Aflatoxin B1	increases methylation, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TL8-506	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diallyl trisulfide	increases expression	1

ChEMBL screening assays

334 unique, capped per target: 329 binding, 3 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1036883	Binding	Inhibition of human MGL activity using [3H]2-oleoylglycerol substrate at 10 nM measured upto 1 hr by high dilution reversibility assay	Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors. — J Med Chem
CHEMBL4201497	ADMET	Stability assessed as human MGL-mediated compound hydrolysis by HPLC analysis	( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes. — J Med Chem
CHEMBL5304996	Functional	[3H] 2-OG cleavage activity assay (HeLa)	Data for DCP probe JNJ-42226314

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1TJ	Abcam U-87MG MGLL KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.