Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62C942)

• DOT Name: DEP domain-containing protein 7 (DEPDC7)
• Synonyms: Protein TR2/D15
• Gene Name: DEPDC7
• Related Disease:
  Depression
  Parkinson disease
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: DEPD7_HUMAN
• Pfam ID: PF00610
• Sequence:
  MATVQEKAAALNLSALHSPAHRPPGFSVAQKPFGATYVWSSIINTLQTQVEVKKRRHRLK
  RHNDCFVGSEAVDVIFSHLIQNKYFGDVDIPRAKVVRVCQALMDYKVFEAVPTKVFGKDK
  KPTFEDSSCSLYRFTTIPNQDSQLGKENKLYSPARYADALFKSSDIRSASLEDLWENLSL
  KPANSPHVNISATLSPQVINEVWQEETIGRLLQLVDLPLLDSLLKQQEAVPKIPQPKRQS
  TMVNSSNYLDRGILKAYSDSQEDEWLSAAIDCLEYLPDQMVVEISRSFPEQPDRTDLVKE
  LLFDAIGRYYSSREPLLNHLSDVHNGIAELLVNGKTEIALEATQLLLKLLDFQNREEFRR
  LLYFMAVAANPSEFKLQKESDNRMVVKRIFSKAIVDNKNLSKGKTDLLVLFLMDHQKDVF
  KIPGTLHKIVSVKLMAIQNGRDPNRDAGYIYCQRIDQRDYSNNTEKTTKDELLNLLKTLD
  EDSKLSAKEKKKLLGQFYKCHPDIFIEHFGD
• Tissue Specificity: Expressed in liver.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Posttranslational Modification	[1]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[3]
Liver cancer	DISDE4BI	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DEP domain-containing protein 7 (DEPDC7).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DEP domain-containing protein 7 (DEPDC7).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DEP domain-containing protein 7 (DEPDC7).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of DEP domain-containing protein 7 (DEPDC7).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DEP domain-containing protein 7 (DEPDC7).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of DEP domain-containing protein 7 (DEPDC7).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of DEP domain-containing protein 7 (DEPDC7).	[14]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DEP domain-containing protein 7 (DEPDC7).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of DEP domain-containing protein 7 (DEPDC7).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DEP domain-containing protein 7 (DEPDC7).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DEP domain-containing protein 7 (DEPDC7).	[20]

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 decreases the methylation of DEP domain-containing protein 7 (DEPDC7).	[16]

References

• [1] Further evidence of DEPDC7 DNA hypomethylation in depression: A study in adult twins.Eur Psychiatry. 2015 Sep;30(6):715-8. doi: 10.1016/j.eurpsy.2015.04.001. Epub 2015 May 4.
• [2] Tomoregulin-2 is found extensively in plaques in Alzheimer's disease brain.J Neurochem. 2006 Jul;98(1):34-44. doi: 10.1111/j.1471-4159.2006.03801.x.
• [3] DEPDC7 inhibits cell proliferation, migration and invasion in hepatoma cells.Oncol Lett. 2017 Dec;14(6):7332-7338. doi: 10.3892/ol.2017.7128. Epub 2017 Oct 3.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] 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.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [15] 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.
• [16] 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.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.
• [19] 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.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.