Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSDOX4Q)

• DOT Name: Beta-2 adrenergic receptor (ADRB2)
• Synonyms: Beta-2 adrenoreceptor; Beta-2 adrenoceptor
• Gene Name: ADRB2
• UniProt ID: ADRB2_HUMAN
• PDB ID: 1GQ4 ; 2R4R ; 2R4S ; 2RH1 ; 3D4S ; 3KJ6 ; 3NY8 ; 3NY9 ; 3NYA ; 3P0G ; 3PDS ; 3SN6 ; 4GBR ; 4LDE ; 4LDL ; 4LDO ; 4QKX ; 5D5A ; 5D5B ; 5D6L ; 5JQH ; 5X7D ; 6E67 ; 6KR8 ; 6MXT ; 6N48 ; 6NI3 ; 6OBA ; 6PRZ ; 6PS0 ; 6PS1 ; 6PS2 ; 6PS3 ; 6PS4 ; 6PS5 ; 6PS6 ; 7BZ2 ; 7DHI ; 7DHR ; 7XK9 ; 7XKA ; 8JJ8 ; 8JJO
• Pfam ID: PF00001
• Sequence:
  MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
  FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
  IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
  AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
  HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
  NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
  GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
• Function: Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  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)
  Ub-specific processing proteases (R-HSA-5689880)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Adrenoceptors (R-HSA-390696)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 9 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Beta-2 adrenergic receptor (ADRB2) affects the response to substance of Aspirin.	[43]
Salbutamol	DMN9CWF	Approved	Beta-2 adrenergic receptor (ADRB2) decreases the response to substance of Salbutamol.	[44]
Dobutamine	DMD1B8Z	Approved	Beta-2 adrenergic receptor (ADRB2) affects the response to substance of Dobutamine.	[45]
Metoprolol	DMOJ0V6	Approved	Beta-2 adrenergic receptor (ADRB2) affects the response to substance of Metoprolol.	[46]
Terbutaline	DMD4381	Approved	Beta-2 adrenergic receptor (ADRB2) increases the response to substance of Terbutaline.	[47]
Benazepril	DMH1M9B	Approved	Beta-2 adrenergic receptor (ADRB2) affects the response to substance of Benazepril.	[48]
Formoterol	DMSOURV	Approved	Beta-2 adrenergic receptor (ADRB2) increases the Surgical and medical procedures ADR of Formoterol.	[49]
Methylphenidate	DM7SJD6	Approved	Beta-2 adrenergic receptor (ADRB2) increases the Hepatotoxicity ADR of Methylphenidate.	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Beta-2 adrenergic receptor (ADRB2) increases the response to substance of Benzo(a)pyrene.	[50]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	Beta-2 adrenergic receptor (ADRB2) increases the chemical synthesis of [3H]cAMP.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Beta-2 adrenergic receptor (ADRB2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-2 adrenergic receptor (ADRB2).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Beta-2 adrenergic receptor (ADRB2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Beta-2 adrenergic receptor (ADRB2).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Beta-2 adrenergic receptor (ADRB2).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Beta-2 adrenergic receptor (ADRB2).	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[12]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Beta-2 adrenergic receptor (ADRB2).	[13]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Beta-2 adrenergic receptor (ADRB2).	[14]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[14]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[15]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Beta-2 adrenergic receptor (ADRB2).	[16]
Ergotidine	DM78IME	Approved	Ergotidine increases the activity of Beta-2 adrenergic receptor (ADRB2).	[17]
Propranolol	DM79NTF	Approved	Propranolol decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[18]
Imipramine	DM2NUH3	Approved	Imipramine decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[19]
Epinephrine	DM3KJBC	Approved	Epinephrine increases the activity of Beta-2 adrenergic receptor (ADRB2).	[20]
Atenolol	DMNKG1Z	Approved	Atenolol increases the expression of Beta-2 adrenergic receptor (ADRB2).	[23]
Salmeterol	DMIEU69	Approved	Salmeterol decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[24]
Labetalol	DMK8U72	Approved	Labetalol decreases the activity of Beta-2 adrenergic receptor (ADRB2).	[25]
Arformoterol	DMYM974	Approved	Arformoterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Fenoterol	DMIP3ZV	Approved	Fenoterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Bambuterol	DMKLSHF	Approved	Bambuterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Pindolol	DMD2NV7	Approved	Pindolol decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[28]
Clenbuterol	DMCKYZ5	Approved	Clenbuterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Vilanterol	DMF5EK1	Approved	Vilanterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Pirbuterol	DMI5678	Approved	Pirbuterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Indacaterol	DMQJHR7	Approved	Indacaterol increases the activity of Beta-2 adrenergic receptor (ADRB2).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Beta-2 adrenergic receptor (ADRB2).	[29]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate increases the expression of Beta-2 adrenergic receptor (ADRB2).	[30]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Beta-2 adrenergic receptor (ADRB2).	[34]
BUTAPROST	DMVYNJZ	Patented	BUTAPROST increases the expression of Beta-2 adrenergic receptor (ADRB2).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Beta-2 adrenergic receptor (ADRB2).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Beta-2 adrenergic receptor (ADRB2).	[37]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Beta-2 adrenergic receptor (ADRB2).	[38]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Beta-2 adrenergic receptor (ADRB2).	[35]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[39]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[40]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Beta-2 adrenergic receptor (ADRB2).	[35]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine decreases the expression of Beta-2 adrenergic receptor (ADRB2).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carvedilol	DMHTEAO	Approved	Carvedilol increases the phosphorylation of Beta-2 adrenergic receptor (ADRB2).	[21]
Alprostadil	DMWH7NQ	Approved	Alprostadil increases the phosphorylation of Beta-2 adrenergic receptor (ADRB2).	[26]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Beta-2 adrenergic receptor (ADRB2).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Norepinephrine	DMOUC09	Approved	Norepinephrine affects the binding of Beta-2 adrenergic receptor (ADRB2).	[22]
ICI 118,551	DM3OU54	Phase 3	ICI 118,551 affects the binding of Beta-2 adrenergic receptor (ADRB2).	[31]
Spermidine	DMVJNFI	Phase 3	Spermidine affects the binding of Beta-2 adrenergic receptor (ADRB2).	[32]
Spermine	DMD4BFY	Terminated	Spermine affects the binding of Beta-2 adrenergic receptor (ADRB2).	[32]
[3H]CGP12177	DMZN1A3	Investigative	[3H]CGP12177 affects the binding of Beta-2 adrenergic receptor (ADRB2).	[41]
Cyanopindolol	DMIBLGH	Investigative	Cyanopindolol affects the binding of Beta-2 adrenergic receptor (ADRB2).	[41]
iodocyanopindolol	DMOA2J8	Investigative	iodocyanopindolol affects the binding of Beta-2 adrenergic receptor (ADRB2).	[42]

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