Details of Drug Off-Target (DOT)

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

• DOT Name: Glutathione S-transferase C-terminal domain-containing protein (GSTCD)
• Gene Name: GSTCD
• Related Disease:
  Acute myocardial infarction
  High blood pressure
  Prostate cancer
  Prostate neoplasm
  Chronic obstructive pulmonary disease
• UniProt ID: GSTCD_HUMAN
• Pfam ID: PF13679
• Sequence:
  MKAIKKSLTEEEYLYLDFSHQTEGCIFPLHTSVTLFLLSYCDCKIFKICLVVTKEVSRDS
  SLLRDDLIQDVEIQIISRQELPPIVQNCCLPAVVERSDNFCRAGLAVVLRHIIQKSYEAD
  PLKKELLELLGFKKTCLKACAEVSQWTRLCELTIPLAIENFLRESSDQPPTIPVEILQLE
  KKLSEPVRVHNDDKLRRQKLKQQKADGVGPPLTKGKAKSKVHTQETSEGLDSSSKSLELK
  VAFSKLTVQEEPATTNREPSHIRKAKASDLPPLEHVFAEGLYFTLADIVLLPCIHHFLVI
  ISRKFSEKLVEFPLLASWYQRIQEVPGVKTAASKCGIQFLHLPKLLTTSTEQHPNLCEVP
  GVEEQSDPLFIGGPRPTMAKLMEKGIEVMFSPHPCPTWTLDWNVLPAAVSPKEGKMSSDR
  ALRKQQQLNNLVYVVTNQAKPGDRIVDFCSGGGHVGIVLAHMLPSCQVTLIENKELSLIR
  AKKRSDELGLSNIWFIQANMEYFTGMFNIGVALHACGVATDMVIEHCIKTRASFVTCPCC
  YGFIQNTSKFNFPKSEQFKKTLSYKEHMILCRFADQTAVQLPPQRRLIGKQCMCLVDLDR
  ARAAEECGYSVQVISMEPESCSPKNNMIVGVPI
• Tissue Specificity: Widely expressed in cell types relevant to airway function, including airway smooth muscle cells and epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Glutathione S-transferase C-terminal domain-containing protein (GSTCD).	[16]

References

• [1] Interaction effects of long-term air pollution exposure and variants in the GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and hypertension: a case-control study.PLoS One. 2014 Jun 10;9(6):e99043. doi: 10.1371/journal.pone.0099043. eCollection 2014.
• [2] Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer.Pharmacogenet Genomics. 2011 Oct;21(10):615-23. doi: 10.1097/FPC.0b013e3283493a57.
• [3] Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.Nat Genet. 2017 Mar;49(3):426-432. doi: 10.1038/ng.3752. Epub 2017 Feb 6.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 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.
• [6] 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.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] 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.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] 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.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [13] 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.
• [14] 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.
• [15] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [16] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.