Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT94WT5X)

• DOT Name: Prostate tumor-overexpressed gene 1 protein (PTOV1)
• Synonyms: PTOV-1; Activator interaction domain-containing protein 2
• Gene Name: PTOV1
• Related Disease:
  Lung adenocarcinoma
  Adenocarcinoma
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Benign prostatic hyperplasia
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiac disease
  Chikungunya virus infection
  Epilepsy
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Essential thrombocythemia
  Gastric cancer
  Gastric neoplasm
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Laryngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Prostate neoplasm
  Transitional cell carcinoma
  Urothelial carcinoma
  Laryngeal squamous cell carcinoma
  Nasopharyngeal carcinoma
  Advanced cancer
  Castration-resistant prostate carcinoma
  Colon carcinoma
  Helicoid peripapillary chorioretinal degeneration
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PTOV1_HUMAN
• Pfam ID: PF11232
• Sequence:
  MVRPRRAPYRSGAGGPLGGRGRPPRPLVVRAVRSRSWPASPRGPQPPRIRARSAPPMEGA
  RVFGALGPIGPSSPGLTLGGLAVSEHRLSNKLLAWSGVLEWQEKRRPYSDSTAKLKRTLP
  CQAYVNQGENLETDQWPQKLIMQLIPQQLLTTLGPLFRNSQLAQFHFTNRDCDSLKGLCR
  IMGNGFAGCMLFPHISPCEVRVLMLLYSSKKKIFMGLIPYDQSGFVSAIRQVITTRKQAV
  GPGGVNSGPVQIVNNKFLAWSGVMEWQEPRPEPNSRSKRWLPSHVYVNQGEILRTEQWPR
  KLYMQLIPQQLLTTLVPLFRNSRLVQFHFTKDLETLKSLCRIMDNGFAGCVHFSYKASCE
  IRVLMLLYSSEKKIFIGLIPHDQGNFVNGIRRVIANQQQVLQRNLEQEQQQRGMGG
• Function: May activate transcription. Required for nuclear translocation of FLOT1. Promotes cell proliferation.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, placenta, skeletal muscle and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Altered Expression	[8]
Cardiac disease	DISVO1I5	Strong	Biomarker	[9]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[10]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[12]
Essential thrombocythemia	DISWWK11	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[14]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[19]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[19]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[20]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[21]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[22]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[23]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[7]
Helicoid peripapillary chorioretinal degeneration	DISFSS5N	Limited	Biomarker	[24]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[23]
Prostate cancer	DISF190Y	Limited	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Prostate tumor-overexpressed gene 1 protein (PTOV1) affects the response to substance of Methotrexate.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[28]
Selenium	DM25CGV	Approved	Selenium increases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[30]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Prostate tumor-overexpressed gene 1 protein (PTOV1).	[32]

References

• [1] Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis.Mutat Res. 1997 Jun;386(3):263-77. doi: 10.1016/s1383-5742(97)00008-2.
• [2] PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks.Oncogene. 2001 Mar 22;20(12):1455-64. doi: 10.1038/sj.onc.1204233.
• [3] PTOV1: a novel testosterone-induced atherogenic gene in human aorta.J Pathol. 2006 Aug;209(4):522-31. doi: 10.1002/path.1993.
• [4] Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane.Molecules. 2017 May 25;22(6):848. doi: 10.3390/molecules22060848.
• [5] Valproic acid, a molecular lead to multiple regulatory pathways.Folia Biol (Praha). 2007;53(2):37-49.
• [6] Novel effect and the mechanistic insights of fruiting body extract of medicinal fungus Antrodia cinnamomea against T47D breast cancer.Phytomedicine. 2017 Jan 15;24:39-48. doi: 10.1016/j.phymed.2016.11.006. Epub 2016 Nov 8.
• [7] A novel DNA-binding motif in prostate tumor overexpressed-1 (PTOV1) required for the expression of ALDH1A1 and CCNG2 in cancer cells.Cancer Lett. 2019 Jun 28;452:158-167. doi: 10.1016/j.canlet.2019.03.019. Epub 2019 Mar 25.
• [8] PTOV-1, a novel protein overexpressed in prostate cancer, shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle.Am J Pathol. 2003 Mar;162(3):897-905. doi: 10.1016/S0002-9440(10)63885-0.
• [9] Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects of rooibos flavonoids and phenylpyruvic acid-2-O--D-glucoside.Nutr Metab (Lond). 2017 Jul 10;14:45. doi: 10.1186/s12986-017-0200-8. eCollection 2017.
• [10] Spectral characterisation, antiviral activities, in silico ADMET and molecular docking of the compounds isolated from Tectona grandis to chikungunya virus.Biomed Pharmacother. 2017 Mar;87:302-310. doi: 10.1016/j.biopha.2016.12.069. Epub 2017 Jan 4.
• [11] Increased PTOV1 expression is related to poor prognosis in epithelial ovarian cancer.Tumour Biol. 2015 Jan;36(1):453-8. doi: 10.1007/s13277-014-2662-x. Epub 2014 Oct 1.
• [12] Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma.Tumour Biol. 2017 Jun;39(6):1010428317705013. doi: 10.1177/1010428317705013.
• [13] Electron Transfer from Bi-Isonicotinic Acid Emerges upon Photodegradation of N3-Sensitized TiO(2) Electrodes.ACS Appl Mater Interfaces. 2017 Oct 11;9(40):35376-35382. doi: 10.1021/acsami.7b08986. Epub 2017 Sep 25.
• [14] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [15] Prostate tumor overexpressed 1 is a novel prognostic marker for hepatocellular carcinoma progression and overall patient survival.Medicine (Baltimore). 2015 Jan;94(4):e423. doi: 10.1097/MD.0000000000000423.
• [16] Autophagy inhibition as a promising therapeutic target for laryngeal cancer.Carcinogenesis. 2019 Dec 31;40(12):1525-1534. doi: 10.1093/carcin/bgz080.
• [17] Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits.J Exp Clin Cancer Res. 2019 Aug 6;38(1):341. doi: 10.1186/s13046-019-1349-y.
• [18] 2-OHOA supplementation reduced adiposity and improved cardiometabolic risk to a greater extent than n-3 PUFA in obese mice.Obes Res Clin Pract. 2019 Nov-Dec;13(6):579-585. doi: 10.1016/j.orcp.2019.10.009. Epub 2019 Nov 29.
• [19] Prostate tumor overexpressed 1 expression in invasive urothelial carcinoma.J Cancer Res Clin Oncol. 2016 May;142(5):937-47. doi: 10.1007/s00432-015-2107-y. Epub 2016 Jan 8.
• [20] Prostate tumor overexpressed-1, in conjunction with human papillomavirus status, predicts outcome in early-stage human laryngeal squamous cell carcinoma.Oncotarget. 2016 May 31;7(22):31878-91. doi: 10.18632/oncotarget.8103.
• [21] Prostate Tumor Overexpressed 1 (PTOV1) Is a Novel Prognostic Marker for Nasopharyngeal Carcinoma Progression and Poor Survival Outcomes.PLoS One. 2015 Aug 25;10(8):e0136448. doi: 10.1371/journal.pone.0136448. eCollection 2015.
• [22] Design and synthesis of 4-piperazinyl quinoline derived urea/thioureas for anti-breast cancer activity by a hybrid pharmacophore approach.J Enzyme Inhib Med Chem. 2019 Dec;34(1):620-630. doi: 10.1080/14756366.2019.1571055.
• [23] Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells.Oncotarget. 2017 Jul 22;8(35):59165-59180. doi: 10.18632/oncotarget.19467. eCollection 2017 Aug 29.
• [24] Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts.Int J Mol Sci. 2017 Nov 24;18(12):2517. doi: 10.3390/ijms18122517.
• [25] The role of prostate tumor overexpressed 1 in cancer progression.Oncotarget. 2017 Feb 14;8(7):12451-12471. doi: 10.18632/oncotarget.14104.
• [26] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [27] 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.
• [28] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [29] 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.
• [30] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [31] 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.
• [32] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [33] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [34] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.