Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-2B adrenergic receptor (ADRA2B)
• Synonyms: Alpha-2 adrenergic receptor subtype C2; Alpha-2B adrenoreceptor; Alpha-2B adrenoceptor; Alpha-2BAR
• Gene Name: ADRA2B
• Related Disease:
  Benign adult familial myoclonic epilepsy
  Epilepsy, familial adult myoclonic, 2
• UniProt ID: ADA2B_HUMAN
• PDB ID: 6K41; 6K42
• Pfam ID: PF00001
• Sequence:
  MDHQDPYSVQATAAIAAAITFLILFTIFGNALVILAVLTSRSLRAPQNLFLVSLAAADIL
  VATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY
  NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPRGRPQCKLNQEAWYILASSIGS
  FFAPCLIMILVYLRIYLIAKRSNRRGPRAKGGPGQGESKQPRPDHGGALASAKLPALASV
  ASAREVNGHSKSTGEKEEGETPEDTGTRALPPSWAALPNSGQGQKEGVCGASPEDEAEEE
  EEEEEEEEECEPQAVPVSPASACSPPLQQPQGSRVLATLRGQVLLGRGVGAIGGQWWRRR
  AQLTREKRFTFVLAVVIGVFVLCWFPFFFSYSLGAICPKHCKVPHGLFQFFFWIGYCNSS
  LNPVIYTIFNQDFRRAFRRILCRPWTQTAW
• Function: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  Adrenaline signalling through Alpha-2 adrenergic receptor (R-HSA-392023)
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  Adrenoceptors (R-HSA-390696)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign adult familial myoclonic epilepsy	DISIMWOV	Supportive	Autosomal dominant	[1]
Epilepsy, familial adult myoclonic, 2	DIS44I9V	Limited	Unknown	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]RX821002	DM6IRN4	Investigative	Alpha-2B adrenergic receptor (ADRA2B) affects the binding of [3H]RX821002.	[9]

1 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 Alpha-2B adrenergic receptor (ADRA2B).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alpha-2B adrenergic receptor (ADRA2B).	[8]

References

• [1] The 2B-adrenergic receptor is mutant in cortical myoclonus and epilepsy. Ann Neurol. 2014 Jan;75(1):77-87. doi: 10.1002/ana.24028. Epub 2014 Jan 2.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [7] 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.
• [8] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [9] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.