Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTS2PH3)

• DTT Name: Dopamine D5 receptor (D5R)
• Synonyms: Dopamine receptor 5; DRD5; D1beta dopamine receptor; D(5)D(1B) dopamine receptor dopamine receptor; D(5) dopamine receptor
• Gene Name: DRD5
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: DRD5_HUMAN
• TTD ID: T46828
• Sequence:
  MLPPGSNGTAYPGQFALYQQLAQGNAVGGSAGAPPLGPSQVVTACLLTLLIIWTLLGNVL
  VCAAIVRSRHLRANMTNVFIVSLAVSDLFVALLVMPWKAVAEVAGYWPFGAFCDVWVAFD
  IMCSTASILNLCVISVDRYWAISRPFRYKRKMTQRMALVMVGLAWTLSILISFIPVQLNW
  HRDQAASWGGLDLPNNLANWTPWEEDFWEPDVNAENCDSSLNRTYAISSSLISFYIPVAI
  MIVTYTRIYRIAQVQIRRISSLERAAEHAQSCRSSAACAPDTSLRASIKKETKVLKTLSV
  IMGVFVCCWLPFFILNCMVPFCSGHPEGPPAGFPCVSETTFDVFVWFGWANSSLNPVIYA
  FNADFQKVFAQLLGCSHFCSRTPVETVNISNELISYNQDIVFHKEIAAAYIHMMPNAVTP
  GNREVDNDEEEGPFDRMFQIYQTSPDGDPVAESVWELDCEGEISLDKITPFTPNGFH
• Function: Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Dopaminergic synapse (hsa04728)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Dopamine receptors (R-HSA-390651)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[1]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LE-300	DMGJL16	Schizophrenia	6A20	Preclinical	[2]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GMC-283	DMT1RH6	Schizophrenia	6A20	Terminated	[2]
ZD-3638	DM6M9GC	Schizophrenia	6A20	Terminated	[2]

17 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-ADTN	DMXWCVY	Discovery agent	N.A.	Investigative	[3]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[4]
1-(4-(4-phenyl-1-piperazinyl)butyl)indolin-2-one	DMM18AQ	Discovery agent	N.A.	Investigative	[5]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine	DMOL2Y0	Discovery agent	N.A.	Investigative	[6]
1-[2-(2-Benzyl-phenoxy)-ethyl]-piperidine	DMTNRG7	Discovery agent	N.A.	Investigative	[1]
1-[2-(2-Benzyl-phenoxy)-ethyl]-pyrrolidine	DMLSU30	Discovery agent	N.A.	Investigative	[1]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine	DMD2NXL	Discovery agent	N.A.	Investigative	[1]
4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine	DM08CG7	Discovery agent	N.A.	Investigative	[1]
beta-ergocriptine	DMU3YXR	Discovery agent	N.A.	Investigative	[3]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[7]
FLUTROLINE	DMUOHVL	Discovery agent	N.A.	Investigative	[8]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[6]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[9]
N-propylnorapomorphine	DMO7MTX	N. A.	N. A.	Investigative	[3]
SKF-83556	DMCMQH8	Discovery agent	N.A.	Investigative	[3]
STEPHOLIDINE	DMGMXQC	Discovery agent	N.A.	Investigative	[10]
[125I]SCH23982	DM06S9X	Discovery agent	N.A.	Investigative	[11]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	2.59E-01	-0.06	-0.18
Schizophrenia	6A20	Superior temporal cortex	8.63E-01	-0.01	-0.08
Type 2 diabetes	5A11	Liver tissue	1.52E-01	-0.14	-1.07

References

• [1] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [2] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [3] Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9.
• [4] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [5] Synthesis of novel lactam derivatives and their evaluation as ligands for the dopamine receptors, leading to a D(4)-selective ligand. Bioorg Med Chem. 2007 Sep 1;15(17):5811-8.
• [6] Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1982 Jul;25(7):855-8.
• [7] Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems. J Med Chem. 1982 Oct;25(10):1133-40.
• [8] Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines. J Med Chem. 1980 Jun;23(6):635-43.
• [9] Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.
• [10] Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities Bioorg Med Chem. 2009 Oct 1;17(19):6898-907.
• [11] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 218).