Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTOG0NK)

• DOT Name: Tumor protein D54 (TPD52L2)
• Synonyms: hD54; Tumor protein D52-like 2
• Gene Name: TPD52L2
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Gastric cancer
  Glioma
  Pancreatic adenocarcinoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Squamous cell carcinoma
  Breast cancer
  Breast carcinoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: TPD54_HUMAN
• Pfam ID: PF04201
• Sequence:
  MDSAGQDINLNSPNKGLLSDSMTDVPVDTGVAARTPAVEGLTEAEEEELRAELTKVEEEI
  VTLRQVLAAKERHCGELKRRLGLSTLGELKQNLSRSWHDVQVSSAYVKTSEKLGEWNEKV
  TQSDLYKKTQETLSQAGQKTSAALSTVGSAISRKLGDMRNSATFKSFEDRVGTIKSKVVG
  DRENGSDNLPSSAGSGDKPLSDPAPF

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[5]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Tumor protein D54 (TPD52L2) affects the binding of PEITC.	[22]

5 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 Tumor protein D54 (TPD52L2).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Tumor protein D54 (TPD52L2).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Tumor protein D54 (TPD52L2).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Tumor protein D54 (TPD52L2).	[19]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Tumor protein D54 (TPD52L2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tumor protein D54 (TPD52L2).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tumor protein D54 (TPD52L2).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor protein D54 (TPD52L2).	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of Tumor protein D54 (TPD52L2).	[15]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Tumor protein D54 (TPD52L2).	[16]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Tumor protein D54 (TPD52L2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor protein D54 (TPD52L2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor protein D54 (TPD52L2).	[20]

References

• [1] Association of Leukemia Target Genes Tet2, Bcl2, and Slc23a2 in Vitamin C Pathways.Cancer Genomics Proteomics. 2019 Sep-Oct;16(5):333-344. doi: 10.21873/cgp.20138.
• [2] Correction to: Retraction of: Tumor Protein D52-Like 2 Contributes to Proliferation of Breast Cancer Cells; 10.10.89/cbr.2014.1723Cancer Biother Radiopharm 2017;32(10):387. DOI: 10.1089/cbr.2014.1723.retract.Cancer Biother Radiopharm. 2018 Oct 1;33(8):361. doi: 10.1089/cbr.2014.1723.retract.correx. Epub 2018 Oct 18.
• [3] Tumor protein D52-like 2 accelerates gastric cancer cell proliferation in vitro.Cancer Biother Radiopharm. 2015 Apr;30(3):111-6. doi: 10.1089/cbr.2014.1766. Epub 2015 Mar 6.
• [4] Lentivirus-mediated knockdown of tumor protein D52-like 2 inhibits glioma cell proliferation.Cell Mol Biol (Noisy-le-grand). 2014 May 11;60(1):39-44.
• [5] MicroRNA-217 inhibits cell proliferation, invasion and migration by targeting Tpd52l2 in human pancreatic adenocarcinoma.Oncol Rep. 2017 Dec;38(6):3567-3573. doi: 10.3892/or.2017.6036. Epub 2017 Oct 16.
• [6] Increased expression of tumor protein D54 is associated with clinical progression and poor prognosis in patients with prostate cancer.Oncol Lett. 2017 Dec;14(6):7739-7744. doi: 10.3892/ol.2017.7214. Epub 2017 Oct 18.
• [7] Tumor protein D54 is a negative regulator of extracellular matrix-dependent migration and attachment in oral squamous cell carcinoma-derived cell lines.Cell Oncol (Dordr). 2013 Jun;36(3):233-45. doi: 10.1007/s13402-013-0131-y. Epub 2013 Mar 26.
• [8] TPD52L2 impacts proliferation, invasiveness and apoptosis of glioblastoma cells via modulation of wnt/-catenin/snail signaling.Carcinogenesis. 2018 Feb 9;39(2):214-224. doi: 10.1093/carcin/bgx125.
• [9] Opposite effects of tumor protein D (TPD) 52 and TPD54 on oral squamous cell carcinoma cells.Int J Oncol. 2017 May;50(5):1634-1646. doi: 10.3892/ijo.2017.3929. Epub 2017 Mar 23.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [14] 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.
• [15] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [16] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [17] 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.
• [18] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [19] 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.
• [20] 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.
• [21] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [22] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.