Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQK3M9X)

• DOT Name: (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4)
• Synonyms: EC 3.1.1.-; Alpha/beta hydrolase domain-containing protein 4; Abhydrolase domain-containing protein 4; Alpha/beta-hydrolase 4
• Gene Name: ABHD4
• UniProt ID: ABHD4_HUMAN
• EC Number: 3.1.1.-
• Pfam ID: PF00561
• Sequence:
  MADDLEQQSQGWLSSWLPTWRPTSMSQLKNVEARILQCLQNKFLARYVSLPNQNKIWTVT
  VSPEQNDRTPLVMVHGFGGGVGLWILNMDSLSARRTLHTFDLLGFGRSSRPAFPRDPEGA
  EDEFVTSIETWRETMGIPSMILLGHSLGGFLATSYSIKYPDRVKHLILVDPWGFPLRPTN
  PSEIRAPPAWVKAVASVLGRSNPLAVLRVAGPWGPGLVQRFRPDFKRKFADFFEDDTISE
  YIYHCNAQNPSGETAFKAMMESFGWARRPMLERIHLIRKDVPITMIYGSDTWIDTSTGKK
  VKMQRPDSYVRDMEIKGASHHVYADQPHIFNAVVEEICDSVD
• Function: Lysophospholipase selective for N-acyl phosphatidylethanolamine (NAPE). Contributes to the biosynthesis of N-acyl ethanolamines, including the endocannabinoid anandamide by hydrolyzing the sn-1 and sn-2 acyl chains from N-acyl phosphatidylethanolamine (NAPE) generating glycerophospho-N-acyl ethanolamine (GP-NAE), an intermediate for N-acyl ethanolamine biosynthesis. Hydrolyzes substrates bearing saturated, monounsaturated, polyunsaturated N-acyl chains. Shows no significant activity towards other lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine.
• Reactome Pathway: Acyl chain remodelling of PE (R-HSA-1482839)
• BioCyc Pathway: MetaCyc:ENSG00000100439-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

19 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 (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[6]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[7]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[8]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[9]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[9]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[9]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of (Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4).	[15]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [8] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [9] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.