Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQW6UAG)

• DOT Name: Keratin, type I cytoskeletal 23 (KRT23)
• Synonyms: Cytokeratin-23; CK-23; Keratin-23; K23
• Gene Name: KRT23
• Related Disease:
  Colon cancer
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Fatty liver disease
  Hepatitis A virus infection
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Gastric cancer
  Stomach cancer
  Adenocarcinoma
  Colon carcinoma
• UniProt ID: K1C23_HUMAN
• Pfam ID: PF00038
• Sequence:
  MNSGHSFSQTPSASFHGAGGGWGRPRSFPRAPTVHGGAGGARISLSFTTRSCPPPGGSWG
  SGRSSPLLGGNGKATMQNLNDRLASYLEKVRALEEANMKLESRILKWHQQRDPGSKKDYS
  QYEENITHLQEQIVDGKMTNAQIILLIDNARMAVDDFNLKYENEHSFKKDLEIEVEGLRR
  TLDNLTIVTTDLEQEVEGMRKELILMKKHHEQEMEKHHVPSDFNVNVKVDTGPREDLIKV
  LEDMRQEYELIIKKKHRDLDTWYKEQSAAMSQEAASPATVQSRQGDIHELKRTFQALEID
  LQTQYSTKSALENMLSETQSRYSCKLQDMQEIISHYEEELTQLRHELERQNNEYQVLLGI
  KTHLEKEITTYRRLLEGESEGTREESKSSMKVSATPKIKAITQETINGRLVLCQVNEIQK
  HA
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[4]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	moderate	Biomarker	[6]
Stomach cancer	DISKIJSX	moderate	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	Disputed	Posttranslational Modification	[1]
Colon carcinoma	DISJYKUO	Disputed	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Keratin, type I cytoskeletal 23 (KRT23) increases the response to substance of Doxorubicin.	[27]
Cisplatin	DMRHGI9	Approved	Keratin, type I cytoskeletal 23 (KRT23) increases the response to substance of Cisplatin.	[27]
Methotrexate	DM2TEOL	Approved	Keratin, type I cytoskeletal 23 (KRT23) increases the response to substance of Methotrexate.	[27]
Paclitaxel	DMLB81S	Approved	Keratin, type I cytoskeletal 23 (KRT23) increases the response to substance of Paclitaxel.	[27]
Topotecan	DMP6G8T	Approved	Keratin, type I cytoskeletal 23 (KRT23) increases the response to substance of Topotecan.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Keratin, type I cytoskeletal 23 (KRT23).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Keratin, type I cytoskeletal 23 (KRT23).	[14]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Keratin, type I cytoskeletal 23 (KRT23).	[16]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[17]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[18]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Keratin, type I cytoskeletal 23 (KRT23).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Keratin, type I cytoskeletal 23 (KRT23).	[26]

References

• [1] Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells.PLoS One. 2013 Sep 9;8(9):e73593. doi: 10.1371/journal.pone.0073593. eCollection 2013.
• [2] Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth.Cell Death Dis. 2017 Jul 27;8(7):e2961. doi: 10.1038/cddis.2017.339.
• [3] Keratin 23 Is a Peroxisome Proliferator-Activated Receptor Alpha-Dependent, MYC-Amplified Oncogene That Promotes Hepatocyte Proliferation.Hepatology. 2019 Jul;70(1):154-167. doi: 10.1002/hep.30530. Epub 2019 Mar 20.
• [4] Gene expression profiling unravels cancer-related hepatic molecular signatures in steatohepatitis but not in steatosis.PLoS One. 2012;7(10):e46584. doi: 10.1371/journal.pone.0046584. Epub 2012 Oct 10.
• [5] Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver.Cells. 2019 Jun 18;8(6):610. doi: 10.3390/cells8060610.
• [6] Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes.Transl Oncol. 2017 Feb;10(1):99-107. doi: 10.1016/j.tranon.2016.11.003. Epub 2016 Dec 22.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [10] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [15] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [19] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [23] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [24] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [27] Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.