Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWG9A4)

• DTT Name: Adrenergic receptor alpha-2A (ADRA2A)
• Synonyms: Alpha-2AAR; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2A adrenergic receptor; Alpha-2 adrenergic receptor subtype C10; ADRAR; ADRA2R
• Gene Name: ADRA2A
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ADA2A_HUMAN
• TTD ID: T11448
• Sequence:
  MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLML
  LTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAW
  CEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVIS
  FPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKR
  RTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGP
  RDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTP
  AAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPR
  TLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV
• Function: 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. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
• KEGG Pathway:
  cGMP-PKG signaling 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 DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Connexyn	DMF29Q5	Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Lofexidine	DM1WXA6	Heroin and opiate withdrawal	6C43	Approved	[2]
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[3]
Guanfacine	DMPN5IH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[4]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[5]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[6]
DSP-1200	DM4WSHG	Depression	6A70-6A7Z	Phase 1	[7]

7 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[8]
NMI-870	DMU596F	Sexual dysfunction	HA00-HA01	Discontinued in Phase 2	[9]
A-80426	DMBC3DG	N. A.	N. A.	Terminated	[10]
S-18616	DMQ8S4L	Pain	MG30-MG3Z	Terminated	[11]
SK&F-104078	DMRADBU	N. A.	N. A.	Terminated	[12]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[13]
WB-4101	DMQU8B1	N. A.	N. A.	Terminated	[14]

67 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[15]
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol	DMF6WHC	Discovery agent	N.A.	Investigative	[16]
(1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amine	DMPKM9B	Discovery agent	N.A.	Investigative	[17]
(1H-Imidazol-2-yl)-quinoxalin-6-yl-amine	DMRDHL2	Discovery agent	N.A.	Investigative	[17]
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine	DM27TH9	Discovery agent	N.A.	Investigative	[17]
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine	DM8N79M	Discovery agent	N.A.	Investigative	[17]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine	DME6MYZ	Discovery agent	N.A.	Investigative	[18]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine	DM5WJBH	Discovery agent	N.A.	Investigative	[18]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine	DMHED9G	Discovery agent	N.A.	Investigative	[18]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline	DM98L2X	Discovery agent	N.A.	Investigative	[19]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline	DMS4JAG	Discovery agent	N.A.	Investigative	[19]
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl	DMFDK4N	Discovery agent	N.A.	Investigative	[20]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline	DMDYX7P	Discovery agent	N.A.	Investigative	[21]
1,2,3,4,5,6-Hexahydro-benzo[c]azocine	DMTKYFE	Discovery agent	N.A.	Investigative	[19]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol	DMHKANE	Discovery agent	N.A.	Investigative	[22]
1,2,3,4-Tetrahydro-isoquinolin-7-ol	DM5VLIE	Discovery agent	N.A.	Investigative	[22]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole	DM3JGVF	Discovery agent	N.A.	Investigative	[23]
1,2,3,4-tetrahydroisoquinoline	DMZGCEQ	Discovery agent	N.A.	Investigative	[24]
1-((S)-2-aminopropyl)-1H-indazol-6-ol	DMU83KP	Discovery agent	N.A.	Investigative	[25]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine	DMWFU3T	Discovery agent	N.A.	Investigative	[20]
1-(pyridin-2-yl)piperazine	DMKE7FG	Discovery agent	N.A.	Investigative	[20]
2,3,4,5-Tetrahydro-1H-benzo[c]azepine	DM1RE9Q	Discovery agent	N.A.	Investigative	[19]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine	DM4EZOB	Discovery agent	N.A.	Investigative	[19]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine	DMOFG4M	Discovery agent	N.A.	Investigative	[19]
2,3-Dihydro-1H-isoindole	DMWI9XS	Discovery agent	N.A.	Investigative	[19]
2-BFi	DMFAW4R	Discovery agent	N.A.	Investigative	[26]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline	DMDPUC7	Discovery agent	N.A.	Investigative	[27]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline	DMH1RX6	Discovery agent	N.A.	Investigative	[16]
3-Methyl-1,2,3,4-tetrahydro-isoquinoline	DMIWQ7G	Discovery agent	N.A.	Investigative	[19]
3-Methyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline	DMZY6VX	Discovery agent	N.A.	Investigative	[28]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole	DMFYBLH	Discovery agent	N.A.	Investigative	[6]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[29]
4-(4-Methyl-indan-1-yl)-1H-imidazole	DMYZHXR	Discovery agent	N.A.	Investigative	[30]
4-Benzo[b]thiophen-4-yl-1H-imidazole	DM02Q8N	Discovery agent	N.A.	Investigative	[31]
5-Aminomethyl-naphthalen-2-ol	DMTP9DB	Discovery agent	N.A.	Investigative	[22]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene	DMNOI7B	Discovery agent	N.A.	Investigative	[19]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline	DMQ1BE8	Discovery agent	N.A.	Investigative	[32]
7-Nitro-1,2,3,4-tetrahydro-isoquinoline	DMX3UV1	Discovery agent	N.A.	Investigative	[28]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline	DMY50UR	Discovery agent	N.A.	Investigative	[22]
AKUAMMIGINE	DMJW4I5	Discovery agent	N.A.	Investigative	[33]
AR-129330	DMUSYKG	Discovery agent	N.A.	Investigative	[34]
Beta-methoxyamphetamine	DMA9CSG	Discovery agent	N.A.	Investigative	[35]
BRL 44408	DM3WPO4	Discovery agent	N.A.	Investigative	[36]
Butyl-indol-1-yl-pyridin-4-yl-amine	DM1CX9Y	Discovery agent	N.A.	Investigative	[18]
C-(6-Methoxy-naphthalen-1-yl)-methylamine	DMJ6SYI	Discovery agent	N.A.	Investigative	[22]
C-Naphthalen-1-yl-methylamine	DMFW1JC	Discovery agent	N.A.	Investigative	[22]
Chloroethylclonidine	DMKZIES	Discovery agent	N.A.	Investigative	[37]
Ciproxifan	DM9N8WM	Dementia	6D80-6D86	Investigative	[38]
Ethyl-indol-1-yl-pyridin-4-yl-amine	DM3CWFR	Discovery agent	N.A.	Investigative	[18]
GNF-PF-2857	DML5QFZ	Discovery agent	N.A.	Investigative	[39]
GNF-PF-3878	DM7BXHQ	Discovery agent	N.A.	Investigative	[39]
Indol-1-yl-methyl-pyridin-4-yl-amine	DMJB876	Discovery agent	N.A.	Investigative	[18]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine	DMR9GNW	Discovery agent	N.A.	Investigative	[18]
Indol-1-yl-pyridin-4-yl-amine	DM1F53L	Discovery agent	N.A.	Investigative	[18]
JP1302	DMMVBK6	Discovery agent	N.A.	Investigative	[39]
METHYLNORADRENALINE	DMOWMPL	Discovery agent	N.A.	Investigative	[14]
MEZILAMINE	DMVYWJS	Discovery agent	N.A.	Investigative	[40]
PIPEROXAN	DMIHO0P	Discovery agent	N.A.	Investigative	[14]
R-226161	DM4BP7S	Discovery agent	N.A.	Investigative	[41]
S-34324	DMZLQ5W	Discovery agent	N.A.	Investigative	[10]
SK&F-29661	DM2KFQ5	Discovery agent	N.A.	Investigative	[28]
SK&F-64139	DM60Y3Q	Discovery agent	N.A.	Investigative	[24]
SNAP-5150	DM2OLGQ	Discovery agent	N.A.	Investigative	[13]
TRACIZOLINE	DM18CV3	Discovery agent	N.A.	Investigative	[32]
Tramazoline	DM3ML0N	Discovery agent	N.A.	Investigative	[14]
TRYPTOLINE	DMV19K7	Discovery agent	N.A.	Investigative	[32]
[3H]RX821002	DM6IRN4	Discovery agent	N.A.	Investigative	[42]

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