Details of Drug Off-Target (DOT)

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

• DOT Name: Sister chromatid cohesion protein DCC1 (DSCC1)
• Synonyms: Defective in sister chromatid cohesion protein 1 homolog
• Gene Name: DSCC1
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Neoplasm
  Polycystic ovarian syndrome
  Hepatocellular carcinoma
• UniProt ID: DCC1_HUMAN
• Pfam ID: PF09724
• Sequence:
  MKRTRDEVDATLQIAKLNAAELLPAVHCLGFGPGASGAAAGDFCLLELEPTLCQQLEDGH
  SLVIRGDKDEQAVLCSKDKTYDLKIADTSNMLLFIPGCKTPDQLKKEDSHCNIIHTEIFG
  FSNNYWELRRRRPKLKKLKKLLMENPYEGPDSQKEKDSNSSKYTTEDLLDQIQASEEEIM
  TQLQVLNACKIGGYWRILEFDYEMKLLNHVTQLVDSESWSFGKVPLNTCLQELGPLEPEE
  MIEHCLKCYGKKYVDEGEVYFELDADKICRAAARMLLQNAVKFNLAEFQEVWQQSVPEGM
  VTSLDQLKGLALVDRHSRPEIIFLLKVDDLPEDNQERFNSLFSLREKWTEEDIAPYIQDL
  CGEKQTIGALLTKYSHSSMQNGVKVYNSRRPIS
• Function: Loads PCNA onto primed templates regulating velocity, spacing and restart activity of replication forks. May couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3.
• Reactome Pathway: Polymerase switching on the C-strand of the telomere (R-HSA-174411)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Sister chromatid cohesion protein DCC1 (DSCC1) affects the response to substance of Doxorubicin.	[22]
Vinblastine	DM5TVS3	Approved	Sister chromatid cohesion protein DCC1 (DSCC1) affects the response to substance of Vinblastine.	[22]
Atorvastatin	DMF28YC	Phase 3 Trial	Sister chromatid cohesion protein DCC1 (DSCC1) affects the response to substance of Atorvastatin.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[15]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[16]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Sister chromatid cohesion protein DCC1 (DSCC1).	[11]

References

• [1] Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer.PLoS One. 2014 Jan 17;9(1):e85750. doi: 10.1371/journal.pone.0085750. eCollection 2014.
• [2] DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) of the Replication Factor Complex CTF18-RFC is Critical for Colon Cancer Cell Growth.J Cancer. 2019 Oct 15;10(24):6142-6153. doi: 10.7150/jca.32339. eCollection 2019.
• [3] Effect of Upregulated DNA Replication and Sister Chromatid Cohesion 1 Expression on Proliferation and Prognosis in Hepatocellular Carcinoma.Chin Med J (Engl). 2018 Dec 5;131(23):2827-2835. doi: 10.4103/0366-6999.246076.
• [4] Commercial Slit Lamp Anterior Segment Photography versus Digital Compact Camera Mounted on a Standard Slit Lamp with an Adapter.Curr Eye Res. 2018 Oct;43(10):1290-1294. doi: 10.1080/02713683.2018.1490435. Epub 2018 Jul 6.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [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] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [19] 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.
• [20] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [21] 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.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [23] Identification of target and pathway of aspirin combined with Lipitor treatment in prostate cancer through integrated bioinformatics analysis. Toxicol Appl Pharmacol. 2022 Oct 1;452:116169. doi: 10.1016/j.taap.2022.116169. Epub 2022 Aug 1.