Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6H1TJ)

• DOT Name: BEN domain-containing protein 6 (BEND6)
• Gene Name: BEND6
• UniProt ID: BEND6_HUMAN
• PDB ID: 7YUL; 7YUN
• Pfam ID: PF10523
• Sequence:
  MQKIVQTDEITNTQAFRKGKRKRTETMDSENANSDMDKGQRDPYSGNAFLPGESSSEDEE
  PLAELSKEELCAKIKSLKEKLTNTRKENSRLRQSLVMLQVLPQAVTQFEELVGMAEALLK
  GGGTMSTSASTLWRATNNSSPDSFASTCSNSNSNSSSPVSLKPEEEHQTDEKQFQIEKWQ
  IARCNKSKPQKFINDLMQVLYTNEYMATHSLTGAKSSTSRDKAVKPAMNQNEVQEIIGVT
  KQLFPNTDDVSIRRMIGQKLNNCTKKPNLSKNLNSQDIK
• Function: Acts as a corepressor of recombining binding protein suppressor hairless (RBPJ) and inhibits Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of BEN domain-containing protein 6 (BEND6).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of BEN domain-containing protein 6 (BEND6).	[6]

9 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 6 (BEND6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of BEN domain-containing protein 6 (BEND6).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of BEN domain-containing protein 6 (BEND6).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of BEN domain-containing protein 6 (BEND6).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of BEN domain-containing protein 6 (BEND6).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of BEN domain-containing protein 6 (BEND6).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BEN domain-containing protein 6 (BEND6).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of BEN domain-containing protein 6 (BEND6).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BEN domain-containing protein 6 (BEND6).	[5]

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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [3] 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.
• [4] 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.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] 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.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.