Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPMG4V7)

• DOT Name: Beta-3 adrenergic receptor (ADRB3)
• Synonyms: Beta-3 adrenoreceptor; Beta-3 adrenoceptor
• Gene Name: ADRB3
• UniProt ID: ADRB3_HUMAN
• Pfam ID: PF00001
• Sequence:
  MAPWPHENSSLAPWPDLPTLAPNTANTSGLPGVPWEAALAGALLALAVLATVGGNLLVIV
  AIAWTPRLQTMTNVFVTSLAAADLVMGLLVVPPAATLALTGHWPLGATGCELWTSVDVLC
  VTASIETLCALAVDRYLAVTNPLRYGALVTKRCARTAVVLVWVVSAAVSFAPIMSQWWRV
  GADAEAQRCHSNPRCCAFASNMPYVLLSSSVSFYLPLLVMLFVYARVFVVATRQLRLLRG
  ELGRFPPEESPPAPSRSLAPAPVGTCAPPEGVPACGRRPARLLPLREHRALCTLGLIMGT
  FTLCWLPFFLANVLRALGGPSLVPGPAFLALNWLGYANSAFNPLIYCRSPDFRSAFRRLL
  CRCGRRLPPEPCAAARPALFPSGVPAARSSPAQPRLCQRLDGASWGVS
• Function: Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
• Tissue Specificity: Expressed mainly in adipose tissues.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Neuroactive ligand-receptor interaction (hsa04080)
  Thermogenesis (hsa04714)
  Regulation of lipolysis in adipocytes (hsa04923)
  Renin secretion (hsa04924)
  Salivary secretion (hsa04970)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Adrenoceptors (R-HSA-390696)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenylephrine	DMZHUO5	Approved	Beta-3 adrenergic receptor (ADRB3) increases the response to substance of Phenylephrine.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	Beta-3 adrenergic receptor (ADRB3) affects the abundance of [3H]cAMP.	[9]

4 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 Beta-3 adrenergic receptor (ADRB3).	[1]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Beta-3 adrenergic receptor (ADRB3).	[2]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the activity of Beta-3 adrenergic receptor (ADRB3).	[3]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Beta-3 adrenergic receptor (ADRB3).	[5]

1 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 Beta-3 adrenergic receptor (ADRB3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]CGP12177	DMZN1A3	Investigative	[3H]CGP12177 affects the binding of Beta-3 adrenergic receptor (ADRB3).	[6]
Cyanopindolol	DMIBLGH	Investigative	Cyanopindolol affects the binding of Beta-3 adrenergic receptor (ADRB3).	[7]

References

• [1] 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.
• [2] Impact of rosiglitazone on the expression of beta3-AR in the stable cell lines expressed beta3-AR gene. Clin Chem Lab Med. 2007;45(11):1511-6. doi: 10.1515/CCLM.2007.315.
• [3] Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human beta3 adrenergic receptor agonists with good oral bioavailability. Part II. J Med Chem. 2008 Jul 10;51(13):4002-20. doi: 10.1021/jm8000345. Epub 2008 Jun 14.
• [4] 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.
• [5] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [6] Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human -adrenoceptors. J Med Chem. 2011 Oct 13;54(19):6874-87. doi: 10.1021/jm2008562. Epub 2011 Sep 16.
• [7] Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells. Naunyn Schmiedebergs Arch Pharmacol. 1999 Apr;359(4):310-21. doi: 10.1007/pl00005357.
• [8] Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management. J Am Coll Cardiol. 2005 Jul 19;46(2):351-9. doi: 10.1016/j.jacc.2005.03.061.
• [9] Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):151-9. doi: 10.1007/s00210-003-0860-y. Epub 2004 Jan 17.