Details of Drug Off-Target (DOT)

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

• DOT Name: Hydroxyacylglutathione hydrolase, mitochondrial (HAGH)
• Synonyms: EC 3.1.2.6; Glyoxalase II; Glx II
• Gene Name: HAGH
• UniProt ID: GLO2_HUMAN
• PDB ID: 1QH3; 1QH5
• EC Number: 3.1.2.6
• Pfam ID: PF16123 ; PF00753
• Sequence:
  MVVGRGLLGRRSLAALGAACARRGLGPALLGVFCHTDLRKNLTVDEGTMKVEVLPALTDN
  YMYLVIDDETKEAAIVDPVQPQKVVDAARKHGVKLTTVLTTHHHWDHAGGNEKLVKLESG
  LKVYGGDDRIGALTHKITHLSTLQVGSLNVKCLATPCHTSGHICYFVSKPGGSEPPAVFT
  GDTLFVAGCGKFYEGTADEMCKALLEVLGRLPPDTRVYCGHEYTINNLKFARHVEPGNAA
  IREKLAWAKEKYSIGEPTVPSTLAEEFTYNPFMRVREKTVQQHAGETDPVTTMRAVRREK
  DQFKMPRD
• Function: Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.
• Tissue Specificity: Expressed in liver and kidney.
• KEGG Pathway:
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[1]

15 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 Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the activity of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[10]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Hydroxyacylglutathione hydrolase, mitochondrial (HAGH).	[14]

References

• [1] 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.
• [2] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Troglitazone selectively inhibits glyoxalase I gene expression. Diabetologia. 2001 Nov;44(11):2004-12. doi: 10.1007/s001250100004.
• [10] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [11] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.