Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6S406I)

• DOT Name: Bestrophin-4 (BEST4)
• Synonyms: Vitelliform macular dystrophy 2-like protein 2
• Gene Name: BEST4
• Related Disease: Colorectal carcinoma
• UniProt ID: BEST4_HUMAN
• Pfam ID: PF01062
• Sequence:
  MTVSYTLKVAEARFGGFSGLLLRWRGSIYKLLYKEFLLFGALYAVLSITYRLLLTQEQRY
  VYAQVARYCNRSADLIPLSFVLGFYVTLVVNRWWSQYTSIPLPDQLMCVISASVHGVDQR
  GRLLRRTLIRYANLASVLVLRSVSTRVLKRFPTMEHVVDAGFMSQEERKKFESLKSDFNK
  YWVPCVWFTNLAAQARRDGRIRDDIALCLLLEELNKYRAKCSMLFHYDWISIPLVYTQVV
  TIAVYSFFALSLVGRQFVEPEAGAAKPQKLLKPGQEPAPALGDPDMYVPLTTLLQFFFYA
  GWLKVAEQIINPFGEDDDDFETNQLIDRNLQVSLLSVDEMYQNLPPAEKDQYWDEDQPQP
  PYTVATAAESLRPSFLGSTFNLRMSDDPEQSLQVEASPGSGRPAPAAQTPLLGRFLGVGA
  PSPAISLRNFGRVRGTPRPPHLLRFRAEEGGDPEAAARIEEESAESGDEALEP
• Function: Forms calcium-sensitive chloride channels. Permeable to bicarbonate.
• Tissue Specificity: Predominantly found in colon and the weakly in fetal brain, spinal cord, retina, lung, trachea, testis and placenta.
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Bestrophin-4 (BEST4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Bestrophin-4 (BEST4).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Bestrophin-4 (BEST4).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Bestrophin-4 (BEST4).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Bestrophin-4 (BEST4).	[4]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Bestrophin-4 (BEST4).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Bestrophin-4 (BEST4).	[9]

2 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 affects the methylation of Bestrophin-4 (BEST4).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Bestrophin-4 (BEST4).	[8]

References

• [1] Prognosis Prediction of Colorectal Cancer Using Gene Expression Profiles.Front Oncol. 2019 Apr 9;9:252. doi: 10.3389/fonc.2019.00252. eCollection 2019.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [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] 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.
• [9] 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.