Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8D40L)

• DOT Name: BEN domain-containing protein 7 (BEND7)
• Gene Name: BEND7
• UniProt ID: BEND7_HUMAN
• Pfam ID: PF10523
• Sequence:
  MEFSERKRSRKSQSFKLVSRDYHHEVYKIPEFSNDVNGEAKETQPIFLGDESMEIKKQIT
  GMRRLLNDSTGRIYQRVGKEGEKLKEEPQDLDLVWPPRLNSSAEAPQSLHPSSRGVWNEL
  PPQSGQFSGQYGTRSRTFQSQPHPTTSSNGELPVVNSSAGSNCCTCNCQSTLQAILQELK
  TMRKLMQIQAVGTQNRQQPPISLICSQRTAVSRKRNKKKKVPPKTVEPLTVKQKPSGSEM
  EKKSVVASELSALQAAEHTSPEESRVLGFGIVLESPSSDPEVQLAEGFDVFMPKSQLDSI
  LSNYTRSGSLLFRKLVCAFFDDKTLANSLPNGKRKRGLNDNRKGLDQNIVGAIKVFTEKY
  CTANHVDKLPGPRDWVQILQDQIKLARRRLKRGSEIADSDERLDGIALPPTGACGGPCTV
  LPGGSAAVTLVLQSSPQTMSQEKGQMAEPWEEQHLVLLNNLTRDRAETGALSQTSQDFKH
  HSFLITQVSATLHHQRGIRNFPTPGSAKSLTLHISCLSL

Molecular Interaction Atlas (MIA) of This DOT

3 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 BEN domain-containing protein 7 (BEND7).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of BEN domain-containing protein 7 (BEND7).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BEN domain-containing protein 7 (BEND7).	[9]

7 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 BEN domain-containing protein 7 (BEND7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BEN domain-containing protein 7 (BEND7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of BEN domain-containing protein 7 (BEND7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BEN domain-containing protein 7 (BEND7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BEN domain-containing protein 7 (BEND7).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of BEN domain-containing protein 7 (BEND7).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BEN domain-containing protein 7 (BEND7).	[10]

References

• [1] 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.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] 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.