Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIWE1WS)

• DOT Name: Monoacylglycerol lipase ABHD6 (ABHD6)
• Synonyms: EC 3.1.1.23; 2-arachidonoylglycerol hydrolase; Abhydrolase domain-containing protein 6
• Gene Name: ABHD6
• UniProt ID: ABHD6_HUMAN
• PDB ID: 7OTS
• EC Number: 3.1.1.23
• Pfam ID: PF00561
• Sequence:
  MDLDVVNMFVIAGGTLAIPILAFVASFLLWPSALIRIYYWYWRRTLGMQVRYVHHEDYQF
  CYSFRGRPGHKPSILMLHGFSAHKDMWLSVVKFLPKNLHLVCVDMPGHEGTTRSSLDDLS
  IDGQVKRIHQFVECLKLNKKPFHLVGTSMGGQVAGVYAAYYPSDVSSLCLVCPAGLQYST
  DNQFVQRLKELQGSAAVEKIPLIPSTPEEMSEMLQLCSYVRFKVPQQILQGLVDVRIPHN
  NFYRKLFLEIVSEKSRYSLHQNMDKIKVPTQIIWGKQDQVLDVSGADMLAKSIANCQVEL
  LENCGHSVVMERPRKTAKLIIDFLASVHNTDNNKKLD
• Function: Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol. Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways. Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids. Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism. BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting.
• KEGG Pathway: Retrograde endocan.binoid sig.ling (hsa04723)
• Reactome Pathway: Arachidonate production from DAG (R-HSA-426048)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Monoacylglycerol lipase ABHD6 (ABHD6).	[13]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.