Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGX2557)

• DOT Name: BET1 homolog (BET1)
• Synonyms: hBET1; Golgi vesicular membrane-trafficking protein p18
• Gene Name: BET1
• Related Disease:
  Abscess
  Acute coronary syndrome
  Atrial fibrillation
  Hyperemesis gravidarum
  Unverricht-Lundborg syndrome
  Uterine fibroids
  High blood pressure
  Influenza
  Arrhythmia
  Bronchiolitis
• UniProt ID: BET1_HUMAN
• PDB ID: 3EGX
• Sequence:
  MRRAGLGEGVPPGNYGNYGYANSGYSACEEENERLTESLRSKVTAIKSLSIEIGHEVKTQ
  NKLLAEMDSQFDSTTGFLGKTMGKLKILSRGSQTKLLCYMMLFSLFVFFIIYWIIKLR
• Function: Required for vesicular transport from the ER to the Golgi complex. Functions as a SNARE involved in the docking process of ER-derived vesicles with the cis-Golgi membrane.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abscess	DISAP982	Strong	Biomarker	[1]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Hyperemesis gravidarum	DIS3YBRD	Strong	Biomarker	[4]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Genetic Variation	[5]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[6]
High blood pressure	DISY2OHH	moderate	Biomarker	[7]
Influenza	DIS3PNU3	moderate	Biomarker	[8]
Arrhythmia	DISFF2NI	Limited	Biomarker	[9]
Bronchiolitis	DISEE9BG	Limited	Biomarker	[10]

1 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 BET1 homolog (BET1).	[11]

11 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 BET1 homolog (BET1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of BET1 homolog (BET1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BET1 homolog (BET1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BET1 homolog (BET1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BET1 homolog (BET1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BET1 homolog (BET1).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of BET1 homolog (BET1).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of BET1 homolog (BET1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BET1 homolog (BET1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of BET1 homolog (BET1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of BET1 homolog (BET1).	[22]

References

• [1] BET 1: Is routine irrigation of a cutaneous abscess necessary?.Emerg Med J. 2018 Feb;35(2):126-127. doi: 10.1136/emermed-2017-207424.2.
• [2] BET 1: IN PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME, DOES WELLENS' SIGN ON THE ELECTROCARDIOGRAPH IDENTIFY CRITICAL LEFT ANTERIOR DESCENDING ARTERY STENOSIS?.Emerg Med J. 2017 Apr;34(4):264-266. doi: 10.1136/emermed-2017-206665.1.
• [3] BET 1: Lenient or strict rate control for atrial fibrillation.Emerg Med J. 2018 Dec;35(12):765-768. doi: 10.1136/emermed-2018-208261.1.
• [4] BET 1: Haloperidol in cannabinoid hyperemesis syndrome.Emerg Med J. 2018 Nov;35(11):711-712. doi: 10.1136/emermed-2018-208170.1.
• [5] Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies.Dis Model Mech. 2017 Dec 19;10(12):1391-1398. doi: 10.1242/dmm.029132.
• [6] Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans.Hum Genet. 2013 Dec;132(12):1361-9. doi: 10.1007/s00439-013-1340-1. Epub 2013 Jul 28.
• [7] Bet 1: Can induced hypertension improve outcome following acute traumatic spinal cord injury?.Emerg Med J. 2018 Apr;35(4):270-272. doi: 10.1136/emermed-2018-207608.2.
• [8] BET 1: Oseltamivir use for quicker alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with influenza B.Emerg Med J. 2019 Jan;36(1):55-56. doi: 10.1136/emermed-2018-208381.1.
• [9] BET 1: What is the incidence of cardiac arrhythmia in adult patients with acute infection prescribed fluoroquinolones?.Emerg Med J. 2019 Oct;36(10):635-638. doi: 10.1136/emermed-2019-208980.2.
• [10] BET 1: High-flow nasal oxygen therapy in bronchiolitis.Emerg Med J. 2019 Apr;36(4):248-249. doi: 10.1136/emermed-2019-208599.1.
• [11] 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.
• [12] 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.
• [13] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [17] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [18] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [19] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [20] 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.
• [21] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [22] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.