Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-2A adrenergic receptor (ADRA2A)
• Synonyms: Alpha-2 adrenergic receptor subtype C10; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2AAR
• Gene Name: ADRA2A
• Related Disease: Lipodystrophy
• UniProt ID: ADA2A_HUMAN
• PDB ID: 1HLL; 1HO9; 1HOD; 1HOF; 6K42; 6KUX; 6KUY; 7EJ0; 7EJ8; 7EJA; 7EJK; 7W6P; 7W7E
• Pfam ID: PF00001
• Sequence:
  MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLML
  LTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAW
  CEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVIS
  FPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKR
  RTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGP
  RDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTP
  AAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPR
  TLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV
• 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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = 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)
  Adrenaline,noradrenaline inhibits insulin secretion (R-HSA-400042)
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  Surfactant metabolism (R-HSA-5683826)
  Adrenoceptors (R-HSA-390696)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lipodystrophy	DIS3SGVD	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ifosfamide	DMCT3I8	Approved	Alpha-2A adrenergic receptor (ADRA2A) increases the Drug tolerance ADR of Ifosfamide.	[24]
Epinephrine	DM3KJBC	Approved	Alpha-2A adrenergic receptor (ADRA2A) increases the Platelet aggregation ADR of Epinephrine.	[24]
Atenolol	DMNKG1Z	Approved	Alpha-2A adrenergic receptor (ADRA2A) affects the response to substance of Atenolol.	[25]
Brimonidine	DMQLT4N	Approved	Alpha-2A adrenergic receptor (ADRA2A) increases the Platelet aggregation ADR of Brimonidine.	[24]
[3H]RX821002	DM6IRN4	Investigative	Alpha-2A adrenergic receptor (ADRA2A) affects the binding of [3H]RX821002.	[14]

3 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-2A adrenergic receptor (ADRA2A).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Alpha-2A adrenergic receptor (ADRA2A).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-2A adrenergic receptor (ADRA2A).	[19]

16 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-2A adrenergic receptor (ADRA2A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Alpha-2A adrenergic receptor (ADRA2A).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[11]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[12]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[13]
Indapamide	DMGN1PW	Approved	Indapamide increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[17]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Alpha-2A adrenergic receptor (ADRA2A).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Oxymetazoline	DM8ZXT6	Approved	Oxymetazoline affects the binding of Alpha-2A adrenergic receptor (ADRA2A).	[14]
Rilmenidine	DM13PQW	Approved	Rilmenidine affects the binding of Alpha-2A adrenergic receptor (ADRA2A).	[16]
Xylometazoline	DMKV32D	Phase 4	Xylometazoline affects the binding of Alpha-2A adrenergic receptor (ADRA2A).	[14]
Phenethylamine	DMX0G4F	Investigative	Phenethylamine affects the binding of Alpha-2A adrenergic receptor (ADRA2A).	[23]

References

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• [16] Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol. 1999 Mar;126(6):1522-30. doi: 10.1038/sj.bjp.0702429.
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• [25] Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment. J Hypertens. 2004 Dec;22(12):2321-8. doi: 10.1097/00004872-200412000-00014.