Details of Drug Off-Target (DOT)

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

• DOT Name: Translationally-controlled tumor protein (TPT1)
• Synonyms: TCTP; Fortilin; Histamine-releasing factor; HRF; p23
• Gene Name: TPT1
• UniProt ID: TCTP_HUMAN
• PDB ID: 1YZ1; 2HR9; 3EBM; 4Z9V; 5O9L; 5O9M; 6IZB; 6IZE
• Pfam ID: PF00838
• Sequence:
  MIIYRDLISHDEMFSDIYKIREIADGLCLEVEGKMVSRTEGNIDDSLIGGNASAEGPEGE
  GTESTVITGVDIVMNHHLQETSFTKEAYKKYIKDYMKSIKGKLEEQRPERVKPFMTGAAE
  QIKHILANFKNYQFFIGENMNPDGMVALLDYREDGVTPYMIFFKDGLEMEKC
• Function: Involved in calcium binding and microtubule stabilization. Acts as a negative regulator of TSC22D1-mediated apoptosis, via interaction with and destabilization of TSC22D1 protein.
• Tissue Specificity: Found in several healthy and tumoral cells including erythrocytes, hepatocytes, macrophages, platelets, keratinocytes, erythroleukemia cells, gliomas, melanomas, hepatoblastomas, and lymphomas. It cannot be detected in kidney and renal cell carcinoma (RCC). Expressed in placenta and prostate.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Translationally-controlled tumor protein (TPT1) decreases the response to substance of Fluorouracil.	[20]
Artesunate	DMR27C8	Approved	Translationally-controlled tumor protein (TPT1) affects the response to substance of Artesunate.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Translationally-controlled tumor protein (TPT1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Translationally-controlled tumor protein (TPT1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Translationally-controlled tumor protein (TPT1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Translationally-controlled tumor protein (TPT1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Translationally-controlled tumor protein (TPT1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Translationally-controlled tumor protein (TPT1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Translationally-controlled tumor protein (TPT1).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Translationally-controlled tumor protein (TPT1).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Translationally-controlled tumor protein (TPT1).	[9]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Translationally-controlled tumor protein (TPT1).	[6]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Translationally-controlled tumor protein (TPT1).	[10]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Translationally-controlled tumor protein (TPT1).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Translationally-controlled tumor protein (TPT1).	[12]
Guaiacol	DMN4E7T	Phase 3	Guaiacol increases the expression of Translationally-controlled tumor protein (TPT1).	[12]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols increases the expression of Translationally-controlled tumor protein (TPT1).	[13]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the expression of Translationally-controlled tumor protein (TPT1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Translationally-controlled tumor protein (TPT1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Translationally-controlled tumor protein (TPT1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Translationally-controlled tumor protein (TPT1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Translationally-controlled tumor protein (TPT1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Translationally-controlled tumor protein (TPT1).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Translationally-controlled tumor protein (TPT1).	[18]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the expression of Translationally-controlled tumor protein (TPT1).	[19]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid increases the expression of Translationally-controlled tumor protein (TPT1).	[12]

References

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• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] 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.
• [5] Detection of gene expression alteration of myeloma cells treated with arsenic trioxide. Zhonghua Xue Ye Xue Za Zhi. 2005 Apr;26(4):209-13.
• [6] Tumor protein translationally controlled 1 is a p53 target gene that promotes cell survival. Cell Cycle. 2013 Jul 15;12(14):2321-8. doi: 10.4161/cc.25404.
• [7] Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. Proteomics. 2009 Apr;9(7):1952-66. doi: 10.1002/pmic.200701089.
• [8] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [9] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [10] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [11] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [12] Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
• [13] Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
• [14] Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis. Am J Cancer Res. 2014 Dec 15;5(1):155-67. eCollection 2015.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Proteomic identification of pterostilbene-mediated anticancer activities in HepG2 cells. Chem Res Toxicol. 2014 Jul 21;27(7):1243-52. doi: 10.1021/tx5001392. Epub 2014 Jul 1.
• [20] Antiapoptotic protein partners fortilin and MCL1 independently protect cells from 5-fluorouracil-induced cytotoxicity. J Biol Chem. 2004 Sep 24;279(39):40868-75. doi: 10.1074/jbc.M401454200. Epub 2004 Jul 15.
• [21] Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Updat. 2005 Feb-Apr;8(1-2):85-97. doi: 10.1016/j.drup.2005.04.003.