Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ES4IE)

• DOT Name: Monoglyceride lipase (MGLL)
• Synonyms: MGL; EC 3.1.1.23; HU-K5; Lysophospholipase homolog; Lysophospholipase-like; Monoacylglycerol lipase; MAGL
• Gene Name: MGLL
• UniProt ID: MGLL_HUMAN
• PDB ID: 3HJU; 3JW8; 3JWE; 3PE6; 4UUQ; 5ZUN; 6AX1; 6BQ0; 7L4T; 7L4U; 7L4W; 7L50; 7PRM; 7ZPG; 8AQF
• EC Number: 3.1.1.23
• Pfam ID: PF12146
• Sequence:
  MPEESSPRRTPQSIPYQDLPHLVNADGQYLFCRYWKPTGTPKALIFVSHGAGEHSGRYEE
  LARMLMGLDLLVFAHDHVGHGQSEGERMVVSDFHVFVRDVLQHVDSMQKDYPGLPVFLLG
  HSMGGAIAILTAAERPGHFAGMVLISPLVLANPESATTFKVLAAKVLNLVLPNLSLGPID
  SSVLSRNKTEVDIYNSDPLICRAGLKVCFGIQLLNAVSRVERALPKLTVPFLLLQGSADR
  LCDSKGAYLLMELAKSQDKTLKIYEGAYHVLHKELPEVTNSVFHEINMWVSQRTATAGTA
  SPP
• 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.
• Tissue Specificity: Detected in adipose tissue, lung, liver, kidney, brain and heart.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway:
  Triglyceride catabolism (R-HSA-163560)
  Arachidonate production from DAG (R-HSA-426048)
  Acyl chain remodeling of DAG and TAG (R-HSA-1482883)
• BioCyc Pathway: MetaCyc:HS01140-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Monoglyceride lipase (MGLL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Monoglyceride lipase (MGLL).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Monoglyceride lipase (MGLL).	[20]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Monoglyceride lipase (MGLL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Monoglyceride lipase (MGLL).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Monoglyceride lipase (MGLL).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Monoglyceride lipase (MGLL).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Monoglyceride lipase (MGLL).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Monoglyceride lipase (MGLL).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Monoglyceride lipase (MGLL).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Monoglyceride lipase (MGLL).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Monoglyceride lipase (MGLL).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Monoglyceride lipase (MGLL).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Monoglyceride lipase (MGLL).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Monoglyceride lipase (MGLL).	[12]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Monoglyceride lipase (MGLL).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Monoglyceride lipase (MGLL).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Monoglyceride lipase (MGLL).	[15]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Monoglyceride lipase (MGLL).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monoglyceride lipase (MGLL).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Monoglyceride lipase (MGLL).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monoglyceride lipase (MGLL).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Monoglyceride lipase (MGLL).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Monoglyceride lipase (MGLL).	[23]

References

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• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
• [14] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [15] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
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• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
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• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.