Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV1XSWG)

• DOT Name: Ornithine decarboxylase antizyme 2 (OAZ2)
• Synonyms: AZ2; ODC-Az 2
• Gene Name: OAZ2
• Related Disease:
  Colon cancer
  Colon carcinoma
  Gastric cancer
  Stomach cancer
  Neuroblastoma
• UniProt ID: OAZ2_HUMAN
• Pfam ID: PF02100
• Sequence:
  MINTQDSSILPLSNCPQLQCCRHIVPGPLWCSDAPHPLSKIPGGRGGGRDPSLSALIYKD
  EKLTVTQDLPVNDGKPHIVHFQYEVTEVKVSSWDAVLSSQSLFVEIPDGLLADGSKEGLL
  ALLEFAEEKMKVNYVFICFRKGREDRAPLLKTFSFLGFEIVRPGHPCVPSRPDVMFMVYP
  LDQNLSDED
• Function: Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity. Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol.
• Reactome Pathway: Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[2]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ornithine decarboxylase antizyme 2 (OAZ2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the methylation of Ornithine decarboxylase antizyme 2 (OAZ2).	[12]

References

• [1] miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells.J Immunol Res. 2018 Aug 2;2018:7498514. doi: 10.1155/2018/7498514. eCollection 2018.
• [2] Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.Gastric Cancer. 2015 Jul;18(3):495-503. doi: 10.1007/s10120-014-0396-5. Epub 2014 Jul 31.
• [3] The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification.Int J Cancer. 2010 May 1;126(9):2012-24. doi: 10.1002/ijc.25074.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
• [13] 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.
• [14] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] 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.