Details of Drug Off-Target (DOT)

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

• DOT Name: S-formylglutathione hydrolase (ESD)
• Synonyms: FGH; EC 3.1.2.12; Esterase D; Methylumbelliferyl-acetate deacetylase; EC 3.1.1.56
• Gene Name: ESD
• Related Disease:
  Adenoma
  Adult glioblastoma
  Aspiration pneumonia
  Aspiration pneumonitis
  Bone osteosarcoma
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Hereditary retinoblastoma
  Malignant soft tissue neoplasm
  Mental disorder
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Polyp
  Sarcoma
  Schizophrenia
  Uveitis
  Bladder cancer
  Stroke
  Type-1 diabetes
  Type-1/2 diabetes
  Congenital contractural arachnodactyly
  Migraine disorder
  Osteoarthritis
  Tuberculosis
• UniProt ID: ESTD_HUMAN
• PDB ID: 3FCX
• EC Number: 3.1.1.56; 3.1.2.12
• Pfam ID: PF00756
• Sequence:
  MALKQISSNKCFGGLQKVFEHDSVELNCKMKFAVYLPPKAETGKCPALYWLSGLTCTEQN
  FISKSGYHQSASEHGLVVIAPDTSPRGCNIKGEDESWDFGTGAGFYVDATEDPWKTNYRM
  YSYVTEELPQLINANFPVDPQRMSIFGHSMGGHGALICALKNPGKYKSVSAFAPICNPVL
  CPWGKKAFSGYLGTDQSKWKAYDATHLVKSYPGSQLDILIDQGKDDQFLLDGQLLPDNFI
  AACTEKKIPVVFRLQEGYDHSYYFIATFITDHIRHHAKYLNA
• Function: Serine hydrolase involved in the detoxification of formaldehyde.
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway: Glutathione conjugation (R-HSA-156590)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Aspiration pneumonia	DIS0DGX4	Strong	Genetic Variation	[3]
Aspiration pneumonitis	DIS5S4DE	Strong	Genetic Variation	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hereditary retinoblastoma	DISPBIDE	Strong	Biomarker	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[4]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Polyp	DISRSLYF	Strong	Biomarker	[10]
Sarcoma	DISZDG3U	Strong	Altered Expression	[4]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[7]
Uveitis	DISV0RYS	Strong	Biomarker	[11]
Bladder cancer	DISUHNM0	moderate	Genetic Variation	[12]
Stroke	DISX6UHX	moderate	Genetic Variation	[13]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[14]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[12]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[15]
Migraine disorder	DISFCQTG	Limited	Genetic Variation	[16]
Osteoarthritis	DIS05URM	Limited	Biomarker	[17]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[18]

15 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 S-formylglutathione hydrolase (ESD).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of S-formylglutathione hydrolase (ESD).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of S-formylglutathione hydrolase (ESD).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of S-formylglutathione hydrolase (ESD).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of S-formylglutathione hydrolase (ESD).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of S-formylglutathione hydrolase (ESD).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of S-formylglutathione hydrolase (ESD).	[25]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of S-formylglutathione hydrolase (ESD).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of S-formylglutathione hydrolase (ESD).	[27]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of S-formylglutathione hydrolase (ESD).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of S-formylglutathione hydrolase (ESD).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of S-formylglutathione hydrolase (ESD).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of S-formylglutathione hydrolase (ESD).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of S-formylglutathione hydrolase (ESD).	[35]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of S-formylglutathione hydrolase (ESD).	[36]

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 S-formylglutathione hydrolase (ESD).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of S-formylglutathione hydrolase (ESD).	[30]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of S-formylglutathione hydrolase (ESD).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of S-formylglutathione hydrolase (ESD).	[33]

References

• [1] Endoscopic full-thickness resection of superficial colorectal neoplasms using a new over-the-scope clip system: A single-centre study.Dig Liver Dis. 2017 Sep;49(9):1009-1013. doi: 10.1016/j.dld.2017.04.015. Epub 2017 May 2.
• [2] A human glioblastoma line with karyotypic nullisomy 13 containing several chromosome 13-specific sequences.Cancer Genet Cytogenet. 1988 Jul 1;33(1):127-32. doi: 10.1016/0165-4608(88)90058-1.
• [3] Preoperative Pulmonary Function Tests Predict Aspiration Pneumonia After Gastric Endoscopic Submucosal Dissection.Dig Dis Sci. 2017 Nov;62(11):3084-3090. doi: 10.1007/s10620-017-4750-4. Epub 2017 Sep 6.
• [4] Chromosome 13 instability and esterase D expression in an osteosarcoma cell line.Cancer Genet Cytogenet. 1987 Feb;24(2):327-34. doi: 10.1016/0165-4608(87)90115-4.
• [5] Risk Factors Associated with Precancerous Lesions of Esophageal Squamous Cell Carcinoma: a Screening Study in a High Risk Chinese Population.J Cancer. 2019 Jun 2;10(14):3284-3290. doi: 10.7150/jca.29979. eCollection 2019.
• [6] Esterase D: evaluation of a potential derived gene marker for hereditary retinoblastoma.Clin Chim Acta. 1988 Mar 31;173(1):81-7. doi: 10.1016/0009-8981(88)90358-0.
• [7] Genetic markers in schizophrenia: ACP1, ESD, TF and GC polymorphisms.Hum Hered. 1990;40(3):136-40. doi: 10.1159/000153920.
• [8] Esterase D assay in Brazilian retinoblastoma families.Am J Med Genet. 1989 Nov;34(3):391-6. doi: 10.1002/ajmg.1320340314.
• [9] Reference genes for gene expression studies on non-small cell lung cancer.Acta Biochim Pol. 2009;56(2):307-16. Epub 2009 Jun 18.
• [10] Sclerotherapy needle injections can expand the subserosal and muscularis propria layers and cause a stable mucosal lift in ESD/EMR patients.Surg Endosc. 2019 Mar;33(3):949-958. doi: 10.1007/s00464-018-6521-5. Epub 2018 Oct 22.
• [11] Proteomic surveillance of retinal autoantigens in endogenous uveitis: implication of esterase D and brain-type creatine kinase as novel autoantigens.Mol Vis. 2008 Jun 12;14:1094-104.
• [12] The esterase D polymorphism in patients with diabetes or carcinoma of the bladder and a matched sample of non-donor controls.Ann Hum Biol. 1978 May;5(3):281-4. doi: 10.1080/03014467800002901.
• [13] Volume-time curve of cardiac magnetic resonance assessed left ventricular dysfunction in coronary artery disease patients with type 2 diabetes mellitus.BMC Cardiovasc Disord. 2017 Jun 5;17(1):145. doi: 10.1186/s12872-017-0583-5.
• [14] HLA, ESD, GLOI, C3 and HP polymorphisms and juvenile insulin dependent diabetes mellitus in Tamil Nadu (south India).Diabetes Res Clin Pract. 1994 Aug;25(1):51-9. doi: 10.1016/0168-8227(94)90161-9.
• [15] Evaluation of anticancer potential of Thai medicinal herb extracts against cholangiocarcinoma cell lines.PLoS One. 2019 May 23;14(5):e0216721. doi: 10.1371/journal.pone.0216721. eCollection 2019.
• [16] Genetic markers: association study in migraine.Cephalalgia. 1995 Jun;15(3):200-4. doi: 10.1046/j.1468-2982.1995.015003200.x.
• [17] Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
• [18] [The use of discrete characters in discriminant analysis for diagnosis of pulmonary tuberculosis and for classification of patients differing in treatment efficiency based on polymorphisms at nine codominant loci-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 and ESD].Genetika. 2003 Jul;39(7):996-1002.
• [19] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [20] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [21] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [28] 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.
• [29] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [30] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [31] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [32] 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.
• [33] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [34] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [35] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [36] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.