Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG40XBT)

• DOT Name: Heme oxygenase 2 (HMOX2)
• Synonyms: HO-2; EC 1.14.14.18
• Gene Name: HMOX2
• UniProt ID: HMOX2_HUMAN
• PDB ID: 2Q32; 2QPP; 2RGZ; 4WMH; 5UC8; 5UC9; 5UCA
• EC Number: 1.14.14.18
• Pfam ID: PF01126
• Sequence:
  MSAEVETSEGVDESEKKNSGALEKENQMRMADLSELLKEGTKEAHDRAENTQFVKDFLKG
  NIKKELFKLATTALYFTYSALEEEMERNKDHPAFAPLYFPMELHRKEALTKDMEYFFGEN
  WEEQVQCPKAAQKYVERIHYIGQNEPELLVAHAYTRYMGDLSGGQVLKKVAQRALKLPST
  GEGTQFYLFENVDNAQQFKQLYRARMNALDLNMKTKERIVEEANKAFEYNMQIFNELDQA
  GSTLARETLEDGFPVHDGKGDMRKCPFYAAEQDKGALEGSSCPFRTAMAVLRKPSLQFIL
  AAGVALAAGLLAWYYM
• Function: [Heme oxygenase 2]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron; [Heme oxygenase 2 soluble form]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Metabolic pathways (hsa01100)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  RHOA GTPase cycle (R-HSA-8980692)
  Iron uptake and transport (R-HSA-917937)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme degradation (R-HSA-189483)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Protoporphyrin IX	DMWYE7A	Investigative	Heme oxygenase 2 (HMOX2) decreases the response to substance of Protoporphyrin IX.	[15]

2 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 Heme oxygenase 2 (HMOX2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Heme oxygenase 2 (HMOX2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heme oxygenase 2 (HMOX2).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Heme oxygenase 2 (HMOX2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heme oxygenase 2 (HMOX2).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heme oxygenase 2 (HMOX2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Heme oxygenase 2 (HMOX2).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Heme oxygenase 2 (HMOX2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heme oxygenase 2 (HMOX2).	[8]
Abexinostat	DM91LGU	Phase 3	Abexinostat decreases the expression of Heme oxygenase 2 (HMOX2).	[9]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Heme oxygenase 2 (HMOX2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Heme oxygenase 2 (HMOX2).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Heme oxygenase 2 (HMOX2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Heme oxygenase 2 (HMOX2).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Heme oxygenase 2 (HMOX2).	[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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [4] 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.
• [5] 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.
• [6] In vitro antioxidant and antigenotoxic potentials of 3,5-O-di-galloylquinic acid extracted from Myrtus communis leaves and modulation of cell gene expression by H2O2. J Appl Toxicol. 2012 May;32(5):333-41.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res. 2009 May 15;15(10):3354-65. doi: 10.1158/1078-0432.CCR-08-2365. Epub 2009 May 5.
• [10] 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.
• [11] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [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] Distinct protective mechanisms of HO-1 and HO-2 against hydroperoxide-induced cytotoxicity. Free Radic Biol Med. 2005 Jan 1;38(1):85-92. doi: 10.1016/j.freeradbiomed.2004.09.031.