Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXPP37T)

• DOT Name: Proline-rich protein 13 (PRR13)
• Synonyms: Taxane-resistance protein
• Gene Name: PRR13
• Related Disease:
  Lung adenocarcinoma
  Epithelial ovarian cancer
  Neoplasm
  Gastric cancer
  Stomach cancer
  Nasopharyngeal carcinoma
• UniProt ID: PRR13_HUMAN
• Sequence:
  MWNPNAGQPGPNPYPPNIGCPGGSNPAHPPPINPPFPPGPCPPPPGAPHGNPAFPPGGPP
  HPVPQPGYPGCQPLGPYPPPYPPPAPGIPPVNPLAPGMVGPAVIVDKKMQKKMKKAHKKM
  HKHQKHHKYHKHGKHSSSSSSSSSSDSD
• Function: Negatively regulates TSP1 expression at the level of transcription. This down-regulation was shown to reduce taxane-induced apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[4]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[5]

10 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 Proline-rich protein 13 (PRR13).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proline-rich protein 13 (PRR13).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Proline-rich protein 13 (PRR13).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Proline-rich protein 13 (PRR13).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Proline-rich protein 13 (PRR13).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proline-rich protein 13 (PRR13).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Proline-rich protein 13 (PRR13).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Proline-rich protein 13 (PRR13).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Proline-rich protein 13 (PRR13).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Proline-rich protein 13 (PRR13).	[15]

References

• [1] Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen.Clin Cancer Res. 2009 Jun 1;15(11):3827-33. doi: 10.1158/1078-0432.CCR-08-3027. Epub 2009 May 12.
• [2] Predictive value of ATP7b, BRCA1, BRCA2, PARP1, UIMC1 (RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) genes in patients with epithelial ovarian cancer who received platinum-taxane first-line therapy.Pharmacogenomics J. 2017 Dec;17(6):506-514. doi: 10.1038/tpj.2016.63. Epub 2016 Oct 25.
• [3] Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression levels between primary tumors and infiltrated regional lymph nodes in patients with resectable non-small cell lung cancer.Pharmacogenomics J. 2019 Feb;19(1):15-24. doi: 10.1038/s41397-018-0013-9. Epub 2018 Feb 22.
• [4] Effects of taxol resistance gene 1 on the cisplatin response in gastric cancer.Oncol Lett. 2018 Jun;15(6):8287-8294. doi: 10.3892/ol.2018.8390. Epub 2018 Mar 30.
• [5] Taxol-Resistant Gene 1 (Txr1) Mediates Oxaliplatin Resistance by Inducing Autophagy in Human Nasopharyngeal Carcinoma Cells.Med Sci Monit. 2019 Jan 16;25:475-483. doi: 10.12659/MSM.913180.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.