Details of Drug Off-Target (DOT)

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

• DOT Name: Glyoxalase domain-containing protein 4 (GLOD4)
• Gene Name: GLOD4
• Related Disease: Hepatocellular carcinoma
• UniProt ID: GLOD4_HUMAN
• PDB ID: 3ZI1
• Pfam ID: PF21701 ; PF21207
• Sequence:
  MAARRALHFVFKVGNRFQTARFYRDVLGMKVESCSVARLECSGAISAHCSDYTRITEDSF
  SKPYDGKWSKTMVGFGPEDDHFVAELTYNYGVGDYKLGNDFMGITLASSQAVSNARKLEW
  PLTEVAEGVFETEAPGGYKFYLQNRSLPQSDPVLKVTLAVSDLQKSLNYWCNLLGMKIYE
  KDEEKQRALLGYADNQCKLELQGVKGGVDHAAAFGRIAFSCPQKELPDLEDLMKRENQKI
  LTPLVSLDTPGKATVQVVILADPDGHEICFVGDEAFRELSKMDPEGSKLLDDAMAADKSD
  EWFAKHNKPKASG
• Tissue Specificity: Expressed in heart, brain, liver, kidney, pancreas and placenta. Not expressed in skeletal muscle and lung.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[6]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[5]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[5]
Gentamicin	DMKINJO	Approved	Gentamicin decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[5]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[9]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Glyoxalase domain-containing protein 4 (GLOD4).	[10]

References

• [1] The promoter analysis of the human C17orf25 gene, a novel chromosome 17p13.3 gene.Cell Res. 2002 Dec;12(5-6):339-52. doi: 10.1038/sj.cr.7290136.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] 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.
• [5] Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
• [6] 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.
• [7] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [8] 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.
• [9] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [10] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.