Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJE9UZY)

• DOT Name: sn-1-specific diacylglycerol lipase ABHD11 (ABHD11)
• Synonyms: EC 3.1.1.116; Alpha/beta hydrolase domain-containing protein 11; Abhydrolase domain-containing protein 11; Williams-Beuren syndrome chromosomal region 21 protein
• Gene Name: ABHD11
• Related Disease:
  Gastric neoplasm
  Thyroid gland papillary carcinoma
  Epithelial ovarian cancer
  Lung adenocarcinoma
• UniProt ID: ABHDB_HUMAN
• EC Number: 3.1.1.116
• Pfam ID: PF00561
• Sequence:
  MLRWTRAWRLPREGLGPHGPSFARVPVAPSSSSGGRGGAEPRPLPLSYRLLDGEAALPAV
  VFLHGLFGSKTNFNSIAKILAQQTGRRVLTVDARNHGDSPHSPDMSYEIMSQDLQDLLPQ
  LGLVPCVVVGHSMGGKTAMLLALQRPELVERLIAVDISPVESTGVSHFATYVAAMRAINI
  ADELPRSRARKLADEQLSSVIQDMAVRQHLLTNLVEVDGRFVWRVNLDALTQHLDKILAF
  PQRQESYLGPTLFLLGGNSQFVHPSHHPEIMRLFPRAQMQTVPNAGHWIHADRPQDFIAA
  IRGFLV
• Function: Catalyzes the hydrolysis of diacylglycerol in vitro and may function as a key regulator in lipid metabolism, namely by regulating the intracellular levels of diacylglycerol. 1,2-diacyl-sn-glycerols are the preferred substrate over 1,3-diacyl-sn-glycerols. The enzyme hydrolyzes stearate in preference to palmitate from the sn-1 position of 1,2-diacyl-sn-glycerols. Maintains the functional lipoylation of the 2-oxoglutarate dehydrogenase complex (OGDHc) through its interaction with the OGDHc by preventing the formation of lipoyl adducts. In addition, is also required for the expansion and differentiation of embryonic stem cells (ESCs).
• Tissue Specificity: Ubiquitously expressed . Highly expressed in small intestine, prostate and thyroid, while aorta and colon tissues exhibit weak expression levels .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Definitive	Altered Expression	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	sn-1-specific diacylglycerol lipase ABHD11 (ABHD11) affects the response to substance of Cisplatin.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[14]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[15]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of sn-1-specific diacylglycerol lipase ABHD11 (ABHD11).	[11]

References

• [1] Increased expression of long noncoding RNA ABHD11-AS1 in gastric cancer and its clinical significance.Med Oncol. 2014 Jul;31(7):42. doi: 10.1007/s12032-014-0042-4.
• [2] Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis.Cell Death Dis. 2019 Aug 14;10(8):620. doi: 10.1038/s41419-019-1850-4.
• [3] lncRNA ABHD11-AS1, regulated by the EGFR pathway, contributes to the ovarian cancer tumorigenesis by epigenetically suppressing TIMP2.Cancer Med. 2019 Nov;8(16):7074-7085. doi: 10.1002/cam4.2586. Epub 2019 Sep 30.
• [4] Human alpha beta hydrolase domain containing protein 11 and its yeast homolog are lipid hydrolases.Biochem Biophys Res Commun. 2017 Jun 10;487(4):875-880. doi: 10.1016/j.bbrc.2017.04.145. Epub 2017 Apr 29.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] 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.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [15] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.