Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSA6U0I)

• DOT Name: Tumor protein D53 (TPD52L1)
• Synonyms: hD53; Tumor protein D52-like 1
• Gene Name: TPD52L1
• Related Disease:
  Breast neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate neoplasm
  Ulcerative colitis
  Breast carcinoma
• UniProt ID: TPD53_HUMAN
• Pfam ID: PF04201
• Sequence:
  MEAQAQGLLETEPLQGTDEDAVASADFSSMLSEEEKEELKAELVQLEDEITTLRQVLSAK
  ERHLVEIKQKLGMNLMNELKQNFSKSWHDMQTTTAYKKTHETLSHAGQKATAAFSNVGTA
  ISKKFGDMSYSIRHSISMPAMRNSPTFKSFEERVETTVTSLKTKVGGTNPNGGSFEEVLS
  STAHASAQSLAGGSRRTKEEELQC
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[5]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Tumor protein D53 (TPD52L1) affects the response to substance of Temozolomide.	[32]
Arsenic trioxide	DM61TA4	Approved	Tumor protein D53 (TPD52L1) decreases the response to substance of Arsenic trioxide.	[33]
DTI-015	DMXZRW0	Approved	Tumor protein D53 (TPD52L1) affects the response to substance of DTI-015.	[32]
Vinblastine	DM5TVS3	Approved	Tumor protein D53 (TPD52L1) affects the response to substance of Vinblastine.	[34]
NAPQI	DM8F5LR	Investigative	Tumor protein D53 (TPD52L1) affects the response to substance of NAPQI.	[35]

34 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 Tumor protein D53 (TPD52L1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor protein D53 (TPD52L1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor protein D53 (TPD52L1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tumor protein D53 (TPD52L1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor protein D53 (TPD52L1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tumor protein D53 (TPD52L1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor protein D53 (TPD52L1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor protein D53 (TPD52L1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tumor protein D53 (TPD52L1).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tumor protein D53 (TPD52L1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tumor protein D53 (TPD52L1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tumor protein D53 (TPD52L1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tumor protein D53 (TPD52L1).	[16]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tumor protein D53 (TPD52L1).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tumor protein D53 (TPD52L1).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Tumor protein D53 (TPD52L1).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Tumor protein D53 (TPD52L1).	[19]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Tumor protein D53 (TPD52L1).	[20]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Tumor protein D53 (TPD52L1).	[21]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Tumor protein D53 (TPD52L1).	[22]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Tumor protein D53 (TPD52L1).	[7]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Tumor protein D53 (TPD52L1).	[7]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Tumor protein D53 (TPD52L1).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tumor protein D53 (TPD52L1).	[14]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Tumor protein D53 (TPD52L1).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tumor protein D53 (TPD52L1).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tumor protein D53 (TPD52L1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor protein D53 (TPD52L1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tumor protein D53 (TPD52L1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tumor protein D53 (TPD52L1).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tumor protein D53 (TPD52L1).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Tumor protein D53 (TPD52L1).	[30]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Tumor protein D53 (TPD52L1).	[31]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Tumor protein D53 (TPD52L1).	[12]

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 Tumor protein D53 (TPD52L1).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Tumor protein D53 (TPD52L1).	[29]

References

• [1] Definition of the tumor protein D52 (TPD52) gene family through cloning of D52 homologues in human (hD53) and mouse (mD52).Genomics. 1996 Aug 1;35(3):523-32. doi: 10.1006/geno.1996.0393.
• [2] Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.Inflamm Bowel Dis. 2013 Mar;19(3):461-70. doi: 10.1097/MIB.0b013e3182802bac.
• [3] TPD52L1-ROS1, a new ROS1 fusion variant in lung adenosquamous cell carcinoma identified by comprehensive genomic profiling.Lung Cancer. 2016 Jul;97:48-50. doi: 10.1016/j.lungcan.2016.04.013. Epub 2016 Apr 22.
• [4] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [5] Nonredundant functions for tumor protein D52-like proteins support specific targeting of TPD52.Clin Cancer Res. 2008 Aug 15;14(16):5050-60. doi: 10.1158/1078-0432.CCR-07-4994.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [8] 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.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [12] Expression profiling of the estrogen responsive genes in response to phytoestrogens using a customized DNA microarray. FEBS Lett. 2005 Mar 14;579(7):1732-40.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [17] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [18] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [19] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [20] 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.
• [21] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [22] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [23] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [24] 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.
• [25] 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.
• [26] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [27] 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.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] 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.
• [30] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [31] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [32] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.
• [33] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.
• [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.
• [35] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.