Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2JJ08Z)

• DOT Name: Proline-rich protein 11 (PRR11)
• Gene Name: PRR11
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: PRR11_HUMAN
• Sequence:
  MPKFKQRRRKLKAKAERLFKKKEASHFQSKLITPPPPPPSPERVGISSIDISQSRSWLTS
  SWNFNFPNIRDAIKLWTNRVWSIYSWCQNCITQSLEVLKDTIFPSRICHRELYSVKQQFC
  ILESKLCKLQEALKTISESSSCPSCGQTCHMSGKLTNVPACVLITPGDSKAVLPPTLPQP
  ASHFPPPPPPPPLPPPPPPLAPVLLRKPSLAKALQAGPLKKDGPMQITVKDLLTVKLKKT
  QSLDEKRKLIPSPKARNPLVTVSDLQHVTLKPNSKVLSTRVTNVLITPGKSQMDLRKLLR
  KVDVERSPGGTPLTNKENMETGTGLTPVMTQALRRKFQLAHPRSPTPTLPLSTSSFDEQN
• Function: Plays a critical role in cell cycle progression.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Genetic Variation	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	moderate	Biomarker	[8]
Stomach cancer	DISKIJSX	moderate	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Proline-rich protein 11 (PRR11).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proline-rich protein 11 (PRR11).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proline-rich protein 11 (PRR11).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proline-rich protein 11 (PRR11).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proline-rich protein 11 (PRR11).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Proline-rich protein 11 (PRR11).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Proline-rich protein 11 (PRR11).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Proline-rich protein 11 (PRR11).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Proline-rich protein 11 (PRR11).	[16]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Proline-rich protein 11 (PRR11).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Proline-rich protein 11 (PRR11).	[18]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Proline-rich protein 11 (PRR11).	[19]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Proline-rich protein 11 (PRR11).	[20]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Proline-rich protein 11 (PRR11).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Proline-rich protein 11 (PRR11).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proline-rich protein 11 (PRR11).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Proline-rich protein 11 (PRR11).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Proline-rich protein 11 (PRR11).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proline-rich protein 11 (PRR11).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Proline-rich protein 11 (PRR11).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Proline-rich protein 11 (PRR11).	[29]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Proline-rich protein 11 (PRR11).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Proline-rich protein 11 (PRR11).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Proline-rich protein 11 (PRR11).	[26]

References

• [1] Proline-rich protein 11 silencing inhibits hepatocellular carcinoma growth and epithelial-mesenchymal transition through -catenin signaling.Gene. 2019 Jan 10;681:7-14. doi: 10.1016/j.gene.2018.09.036. Epub 2018 Sep 21.
• [2] PRR11 and SKA2 gene pair is overexpressed and regulated by p53 in breast cancer.BMB Rep. 2019 Feb;52(2):157-162. doi: 10.5483/BMBRep.2019.52.2.207.
• [3] PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/-Catenin Pathway.Cell Physiol Biochem. 2018;49(2):696-705. doi: 10.1159/000493034. Epub 2018 Aug 30.
• [4] Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma.Onco Targets Ther. 2019 Apr 9;12:2677-2693. doi: 10.2147/OTT.S180255. eCollection 2019.
• [5] Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/-catenin signaling pathway.Oncotarget. 2016 Sep 27;7(39):63449-63455. doi: 10.18632/oncotarget.11523.
• [6] Knockdown of lncRNA DLX6-AS1 inhibits cell proliferation, migration and invasion while promotes apoptosis by downregulating PRR11 expression and upregulating miR-144 in non-small cell lung cancer.Biomed Pharmacother. 2019 Jan;109:1851-1859. doi: 10.1016/j.biopha.2018.09.151. Epub 2018 Nov 26.
• [7] Expression of PRR11 protein and its correlation with pancreatic cancer and effect on survival.Oncol Lett. 2017 Jun;13(6):4117-4122. doi: 10.3892/ol.2017.5974. Epub 2017 Apr 3.
• [8] Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells.Cell Physiol Biochem. 2018;47(4):1721-1728. doi: 10.1159/000491005. Epub 2018 Jul 13.
• [9] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [10] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [11] 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.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [19] 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.
• [20] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [21] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [22] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [23] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] 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.
• [27] 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.
• [28] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [29] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [30] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.