Details of Drug Off-Target (DOT)

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

• DOT Name: Ornithine decarboxylase (ODC1)
• Synonyms: ODC; EC 4.1.1.17
• Gene Name: ODC1
• Related Disease: Neurodevelopmental disorder with alopecia and brain abnormalities
• UniProt ID: DCOR_HUMAN
• PDB ID: 1D7K; 2ON3; 2OO0; 4ZGY; 5BWA; 7S3F; 7S3G; 7U6P; 7U6U
• EC Number: 4.1.1.17
• Pfam ID: PF02784 ; PF00278
• Sequence:
  MNNFGNEEFDCHFLDEGFTAKDILDQKINEVSSSDDKDAFYVADLGDILKKHLRWLKALP
  RVTPFYAVKCNDSKAIVKTLAATGTGFDCASKTEIQLVQSLGVPPERIIYANPCKQVSQI
  KYAANNGVQMMTFDSEVELMKVARAHPKAKLVLRIATDDSKAVCRLSVKFGATLRTSRLL
  LERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPG
  SEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ
  TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTC
  DGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQF
  QNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV
• Function: Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Efferocytosis (hsa04148)
• Reactome Pathway:
  Metabolism of polyamines (R-HSA-351202)
  Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)
• BioCyc Pathway: MetaCyc:HS03935-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodevelopmental disorder with alopecia and brain abnormalities	DISL2H13	Strong	Autosomal dominant	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Ornithine decarboxylase (ODC1) increases the Hepatotoxicity ADR of Acetaminophen.	[43]
Dexamethasone	DMMWZET	Approved	Ornithine decarboxylase (ODC1) increases the Gastrointestinal disorders ADR of Dexamethasone.	[43]
Ifosfamide	DMCT3I8	Approved	Ornithine decarboxylase (ODC1) increases the Metabolic disorder ADR of Ifosfamide.	[43]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Ornithine decarboxylase (ODC1) increases the Metabolic disorder ADR of Chlorpromazine.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ornithine decarboxylase (ODC1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ornithine decarboxylase (ODC1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ornithine decarboxylase (ODC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ornithine decarboxylase (ODC1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ornithine decarboxylase (ODC1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ornithine decarboxylase (ODC1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ornithine decarboxylase (ODC1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the activity of Ornithine decarboxylase (ODC1).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ornithine decarboxylase (ODC1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ornithine decarboxylase (ODC1).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Ornithine decarboxylase (ODC1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ornithine decarboxylase (ODC1).	[13]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ornithine decarboxylase (ODC1).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ornithine decarboxylase (ODC1).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Ornithine decarboxylase (ODC1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ornithine decarboxylase (ODC1).	[4]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Ornithine decarboxylase (ODC1).	[17]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Ornithine decarboxylase (ODC1).	[18]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Ornithine decarboxylase (ODC1).	[4]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Ornithine decarboxylase (ODC1).	[19]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Ornithine decarboxylase (ODC1).	[20]
Propranolol	DM79NTF	Approved	Propranolol increases the activity of Ornithine decarboxylase (ODC1).	[21]
Teniposide	DMLW57T	Approved	Teniposide decreases the expression of Ornithine decarboxylase (ODC1).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ornithine decarboxylase (ODC1).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Ornithine decarboxylase (ODC1).	[24]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Ornithine decarboxylase (ODC1).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Ornithine decarboxylase (ODC1).	[26]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Ornithine decarboxylase (ODC1).	[27]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Ornithine decarboxylase (ODC1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ornithine decarboxylase (ODC1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ornithine decarboxylase (ODC1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ornithine decarboxylase (ODC1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ornithine decarboxylase (ODC1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the activity of Ornithine decarboxylase (ODC1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ornithine decarboxylase (ODC1).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ornithine decarboxylase (ODC1).	[34]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the activity of Ornithine decarboxylase (ODC1).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin increases the activity of Ornithine decarboxylase (ODC1).	[35]
Paraquat	DMR8O3X	Investigative	Paraquat increases the activity of Ornithine decarboxylase (ODC1).	[36]
geraniol	DMS3CBD	Investigative	geraniol decreases the activity of Ornithine decarboxylase (ODC1).	[37]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Ornithine decarboxylase (ODC1).	[38]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Ornithine decarboxylase (ODC1).	[39]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Ornithine decarboxylase (ODC1).	[40]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Ornithine decarboxylase (ODC1).	[4]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the expression of Ornithine decarboxylase (ODC1).	[24]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	Pyrrolidine dithiocarbamate increases the expression of Ornithine decarboxylase (ODC1).	[41]
Formic Acid	DMNFZC6	Investigative	Formic Acid decreases the activity of Ornithine decarboxylase (ODC1).	[9]
METHOCTRAMINE	DMH2CKX	Investigative	METHOCTRAMINE decreases the activity of Ornithine decarboxylase (ODC1).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ornithine decarboxylase (ODC1).	[32]

References

• [1] Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features. Am J Med Genet A. 2018 Dec;176(12):2548-2553. doi: 10.1002/ajmg.a.40523. Epub 2018 Sep 21.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [8] Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis. 2001 Mar;22(3):409-14. doi: 10.1093/carcin/22.3.409.
• [9] Effects of formaldehyde, acetaldehyde, benzoyl peroxide, and hydrogen peroxide on cultured normal human bronchial epithelial cells. Cancer Res. 1985 Jun;45(6):2522-6.
• [10] 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.
• [11] Methotrexate induced differentiation in colon cancer cells is primarily due to purine deprivation. J Cell Biochem. 2006 Sep 1;99(1):146-55. doi: 10.1002/jcb.20908.
• [12] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [13] 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.
• [14] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [17] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [18] DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1. Carcinogenesis. 2004 Jul;25(7):1293-8.
• [19] Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro. PLoS One. 2011;6(9):e24831. doi: 10.1371/journal.pone.0024831. Epub 2011 Sep 14.
• [20] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [21] Adrenergic modulation of cardiac development in the rat: effects of prenatal exposure to propranolol via continuous maternal infusion. J Dev Physiol. 1990 May;13(5):243-9.
• [22] Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells. Biochem Pharmacol. 2001 Sep 1;62(5):593-602. doi: 10.1016/s0006-2952(01)00699-2.
• [23] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [24] Resveratrol-induced modification of polyamine metabolism is accompanied by induction of c-Fos. Carcinogenesis. 2003 Mar;24(3):469-74. doi: 10.1093/carcin/24.3.469.
• [25] 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.
• [26] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [27] Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts. Anticancer Drugs. 2009 Sep;20(8):682-92.
• [28] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [29] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [30] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [31] 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.
• [32] 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.
• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [34] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [35] NADH: ubiquinone oxidoreductase inhibitors block induction of ornithine decarboxylase activity in MCF-7 human breast cancer cells. Pharmacol Toxicol. 1998 Nov;83(5):214-9. doi: 10.1111/j.1600-0773.1998.tb01471.x.
• [36] Pronounced activation of protein kinase C, ornithine decarboxylase and c-jun proto-oncogene by paraquat-generated active oxygen species in WI-38 human lung cells. Biochim Biophys Acta. 1995 Aug 31;1268(2):229-36. doi: 10.1016/0167-4889(95)00076-5.
• [37] Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. J Pharmacol Exp Ther. 2001 Jul;298(1):197-200.
• [38] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [39] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [40] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [41] Effects of a redox-active agent on lymphocyte activation and early gene expression patterns. Free Radic Biol Med. 2004 Nov 15;37(10):1550-63.
• [42] Cytotoxicity of methoctramine and methoctramine-related polyamines. Chem Biol Interact. 2009 Oct 30;181(3):409-16. doi: 10.1016/j.cbi.2009.06.015. Epub 2009 Jul 1.
• [43] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.