Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMZK7XE)

DOT Name	Pescadillo homolog (PES1)
Gene Name	PES1
Related Disease	Diabetic kidney disease ( ) Type-1/2 diabetes ( ) Advanced cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Gastric cancer ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Pancreatic cancer ( ) Periodontal disease ( ) Stomach cancer ( ) Thyroid gland papillary carcinoma ( ) Epithelial ovarian cancer ( ) Hyperglycemia ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Neuroblastoma ( ) Non-insulin dependent diabetes ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pneumonia ( )
UniProt ID	PESC_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2EP8; 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY; 8FKZ; 8FL2; 8FL3; 8FL4; 8FL6; 8FL7; 8FLA; 8FLB; 8FLD; 8FLE; 8INE; 8INF; 8IPX; 8IPY; 8IR3
Pfam ID	PF16589 ; PF06732
Sequence	MGGLEKKKYERGSATNYITRNKARKKLQLSLADFRRLCILKGIYPHEPKHKKKVNKGSTA ARTFYLIKDIRFLLHEPIVNKFREYKVFVRKLRKAYGKSEWNTVERLKDNKPNYKLDHII KERYPTFIDALRDLDDALSMCFLFSTFPRTGKCHVQTIQLCRRLTVEFMHYIIAARALRK VFLSIKGIYYQAEVLGQPIVWITPYAFSHDHPTDVDYRVMATFTEFYTTLLGFVNFRLYQ LLNLHYPPKLEGQAQAEAKAGEGTYALDSESCMEKLAALSASLARVVVPATEEEAEVDEF PTDGEMSAQEEDRRKELEAQEKHKKLFEGLKFFLNREVPREALAFIIRSFGGEVSWDKSL CIGATYDVTDSRITHQIVDRPGQQTSVIGRCYVQPQWVFDSVNARLLLPVAEYFSGVQLP PHLSPFVTEKEGDYVPPEKLKLLALQRGEDPGNLNESEEEEEEDDNNEGDGDEEGENEEE EEDAEAGSEKEEEARLAALEEQRMEGKKPRVMAGTLKLEDKQRLAQEEESEAKRLAIMMM KKREKYLYQKIMFGKRRKIREANKLAEKRKAHDEAVRSEKKAKKARPE
Function	Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.
Tissue Specificity	Significant levels are detected in a variety of cancer cell lines, including glioblastoma, breast carcinoma, colon carcinoma and cervical carcinoma cells. Levels are abnormally elevated in malignant tumors of astrocytic origin.
Reactome Pathway	Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Diabetic kidney disease	DISJMWEY	Definitive	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[3]
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	DISBHBD6	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]
Periodontal disease	DISJQHVN	Strong	Genetic Variation	[9]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[11]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[12]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[13]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[14]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[11]
Pneumonia	DIS8EF3M	Limited	Biomarker	[15]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

9 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 Pescadillo homolog (PES1).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pescadillo homolog (PES1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pescadillo homolog (PES1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pescadillo homolog (PES1).	[19]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Pescadillo homolog (PES1).	[20]
Selenium	DM25CGV	Approved	Selenium increases the expression of Pescadillo homolog (PES1).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Pescadillo homolog (PES1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pescadillo homolog (PES1).	[23]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A decreases the expression of Pescadillo homolog (PES1).	[24]
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⏷ Show the Full List of 9 Drug(s)

1 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 affects the methylation of Pescadillo homolog (PES1).	[22]
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References

1	Nop-7-associated 2 (NSA2), a candidate gene for diabetic nephropathy, is involved in the TGF1 pathway.Int J Biochem Cell Biol. 2013 Mar;45(3):626-35. doi: 10.1016/j.biocel.2012.11.020. Epub 2012 Dec 7.
2	PES1 promotes BET inhibitors resistance and cells proliferation through increasing c-Myc expression in pancreatic cancer.J Exp Clin Cancer Res. 2019 Nov 12;38(1):463. doi: 10.1186/s13046-019-1466-7.
3	PES1 In Liver Cancer: A Prognostic Biomarker With Tumorigenic Roles.Cancer Manag Res. 2019 Nov 14;11:9641-9653. doi: 10.2147/CMAR.S226471. eCollection 2019.
4	PES1 promotes breast cancer by differentially regulating ER and ER.J Clin Invest. 2012 Aug;122(8):2857-70. doi: 10.1172/JCI62676. Epub 2012 Jul 23.
5	A highly soluble matrix metalloproteinase-9 inhibitor for potential treatment of dry eye syndrome.Basic Clin Pharmacol Toxicol. 2012 Nov;111(5):289-95. doi: 10.1111/j.1742-7843.2012.00896.x. Epub 2012 May 18.
6	PES1 is transcriptionally regulated by BRD4 and promotes cell proliferation and glycolysis in hepatocellular carcinoma.Int J Biochem Cell Biol. 2018 Nov;104:1-8. doi: 10.1016/j.biocel.2018.08.014. Epub 2018 Aug 29.
7	PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs.Biochem Biophys Res Commun. 2013 Feb 15;431(3):460-5. doi: 10.1016/j.bbrc.2012.12.145. Epub 2013 Jan 16.
8	PES1 enhances proliferation and tumorigenesis in hepatocellular carcinoma via the PI3K/AKT pathway.Life Sci. 2019 Feb 15;219:182-189. doi: 10.1016/j.lfs.2018.12.054. Epub 2019 Jan 8.
9	Esthetic Assessment of Implants Placed into Fresh Extraction Sockets for Single-Tooth Replacements Using a Flapless Approach.Clin Implant Dent Relat Res. 2017 Apr;19(2):351-364. doi: 10.1111/cid.12458. Epub 2016 Nov 2.
10	PES1 promotes the occurrence and development of papillary thyroid cancer by upregulating the ER/ER protein ratio.Sci Rep. 2019 Jan 31;9(1):1032. doi: 10.1038/s41598-018-37648-7.
11	PES1 differentially regulates the expression of ER and ER in ovarian cancer.IUBMB Life. 2013 Dec;65(12):1017-25. doi: 10.1002/iub.1228. Epub 2013 Nov 24.
12	Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.Nat Genet. 2010 Sep;42(9):759-63. doi: 10.1038/ng.648. Epub 2010 Aug 22.
13	Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation.Cancer Sci. 2015 Mar;106(3):237-43. doi: 10.1111/cas.12598. Epub 2015 Feb 4.
14	Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy.Diabetologia. 2012 Mar;55(3):825-34. doi: 10.1007/s00125-011-2373-4. Epub 2011 Nov 18.
15	Risk factors for drug-resistant pathogens in immunocompetent patients with pneumonia: Evaluation of PES pathogens.J Infect Chemother. 2017 Jan;23(1):23-28. doi: 10.1016/j.jiac.2016.09.002. Epub 2016 Oct 8.
16	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
17	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.
18	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
19	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.
20	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.
21	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.
22	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.
23	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
24	Licochalcone A inhibits cell growth through the downregulation of the Hippo pathway via PES1 in cholangiocarcinoma cells. Environ Toxicol. 2022 Mar;37(3):564-573. doi: 10.1002/tox.23422. Epub 2021 Nov 30.