Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS4R6CX)

• DOT Name: Occludin/ELL domain-containing protein 1 (OCEL1)
• Gene Name: OCEL1
• Related Disease: Aicardi syndrome
• UniProt ID: OCEL1_HUMAN
• Pfam ID: PF07303
• Sequence:
  MHNPDGSASPTADPGSELQTLGQAARRPPPPRAGHDAPRRTRPSARKPLSCFSRRPMPTR
  EPPKTRGSRGHLHTHPPGPGPPLQGLAPRGLKTSAPRPPCQPQPGPHKAKTKKIVFEDEL
  LSQALLGAKKPIGAIPKGHKPRPHPVPDYELKYPPVSSERERSRYVAVFQDQYGEFLELQ
  HEVGCAQAKLRQLEALLSSLPPPQSQKEAQVAARVWREFEMKRMDPGFLDKQARCHYLKG
  KLRHLKTQIQKFDDQGDSEGSVYF

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aicardi syndrome	DISBQXZB	Limited	Autosomal dominant	[1]

15 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 Occludin/ELL domain-containing protein 1 (OCEL1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Occludin/ELL domain-containing protein 1 (OCEL1).	[13]

References

• [1] A De Novo Mutation in TEAD1 Causes Non-X-Linked Aicardi Syndrome. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3896-904. doi: 10.1167/iovs.14-16261.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] 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.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.