Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-1B adrenergic receptor (ADRA1B)
• Synonyms: Alpha-1B adrenoreceptor; Alpha-1B adrenoceptor
• Gene Name: ADRA1B
• UniProt ID: ADA1B_HUMAN
• Pfam ID: PF00001
• Sequence:
  MNPDLDTGHNTSAPAHWGELKNANFTGPNQTSSNSTLPQLDITRAISVGLVLGAFILFAI
  VGNILVILSVACNRHLRTPTNYFIVNLAMADLLLSFTVLPFSAALEVLGYWVLGRIFCDI
  WAAVDVLCCTASILSLCAISIDRYIGVRYSLQYPTLVTRRKAILALLSVWVLSTVISIGP
  LLGWKEPAPNDDKECGVTEEPFYALFSSLGSFYIPLAVILVMYCRVYIVAKRTTKNLEAG
  VMKEMSNSKELTLRIHSKNFHEDTLSSTKAKGHNPRSSIAVKLFKFSREKKAAKTLGIVV
  GMFILCWLPFFIALPLGSLFSTLKPPDAVFKVVFWLGYFNSCLNPIIYPCSSKEFKRAFV
  RILGCQCRGRGRRRRRRRRRLGGCAYTYRPWTRGGSLERSQSRKDSLDDSGSCLSGSQRT
  LPSASPSPGYLGRGAPPPVELCAFPEWKAPGALLSLPAPEPPGRRGRHDSGPLFTFKLLT
  EPESPGTDGGASNGGCEAAADVANGQPGFKSNMPLAPGQF
• Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Neuroactive ligand-receptor interaction (hsa04080)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Salivary secretion (hsa04970)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (12/13) signalling events (R-HSA-416482)
  Adrenoceptors (R-HSA-390696)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
D-myo-inositol 1,4,5-trisphosphate	DMNUKIX	Investigative	Alpha-1B adrenergic receptor (ADRA1B) increases the abundance of D-myo-inositol 1,4,5-trisphosphate.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[6]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[7]
Phenylephrine	DMZHUO5	Approved	Phenylephrine increases the activity of Alpha-1B adrenergic receptor (ADRA1B).	[8]
Epinephrine	DM3KJBC	Approved	Epinephrine increases the activity of Alpha-1B adrenergic receptor (ADRA1B).	[8]
Terbutaline	DMD4381	Approved	Terbutaline increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[6]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the activity of Alpha-1B adrenergic receptor (ADRA1B).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[14]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Alpha-1B adrenergic receptor (ADRA1B).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Alpha-1B adrenergic receptor (ADRA1B).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-1B adrenergic receptor (ADRA1B).	[13]

7 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quinidine	DMLPICK	Approved	Quinidine affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[9]
Phentolamine	DMXYJOB	Approved	Phentolamine affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[8]
Oxymetazoline	DM8ZXT6	Approved	Oxymetazoline affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[10]
Alfuzosin	DMZVMKF	Approved	Alfuzosin affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[11]
Xylometazoline	DMKV32D	Phase 4	Xylometazoline affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[10]
Verapamil	DMA7PEW	Phase 2/3 Trial	Verapamil affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[9]
BMY-7378	DMRHCEG	Terminated	BMY-7378 affects the binding of Alpha-1B adrenergic receptor (ADRA1B).	[15]

References

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• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999 Mar 1;95(1-2):165-73. doi: 10.1016/s0165-5728(99)00011-9.
• [7] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [8] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [9] Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. doi: 10.1161/01.cir.97.13.1227.
• [10] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [11] The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8.
• [12] Characterization of the potent, selective Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one, in cellular and in vivo models of pulmonary oxidative stress. J Pharmacol Exp Ther. 2017 Oct;363(1):114-125.
• [13] 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.
• [14] 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.
• [15] Heterodimers of alpha1B- and alpha1D-adrenergic receptors form a single functional entity. Mol Pharmacol. 2006 Jan;69(1):45-55. doi: 10.1124/mol.105.014985. Epub 2005 Sep 29.
• [16] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.