Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE0A2F)

• DTT Name: Dopamine D4 receptor (D4R)
• Synonyms: DRD4; D(2C)D(4) dopamine receptor dopamine receptor
• Gene Name: DRD4
• DTT Type: Successful target; [1]
• Related Disease:
  Allergic/hypersensitivity disorder [ICD-11: 4A80-4A8Z]
  Schizophrenia [ICD-11: 6A20]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: DRD4_HUMAN
• TTD ID: T24983
• Sequence:
  MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA
  TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT
  ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR
  DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG
  PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPSLPQDPCGPDCAPPAPG
  LPPDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWT
  PFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC
• Function: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Dopamine receptors (R-HSA-390651)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[2]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[3]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[4], [5]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[6]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[7], [8]

8 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[9]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[10]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[11]
A-80426	DMBC3DG	N. A.	N. A.	Terminated	[12]
Belaperidone	DMM0ZIJ	Schizophrenia	6A20	Terminated	[7]
BIMG80	DM9X1DZ	Psychotic disorder	6A20-6A25	Terminated	[13]
Sonepiprazole	DMFI0GW	Schizophrenia	6A20	Terminated	[7]
YM-43611	DMWI094	Psychotic disorder	6A20-6A25	Terminated	[14]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[7]
SPI-376	DMC1WAJ	Schizophrenia	6A20	Preclinical	[7]
U-99363E	DMOIWVC	Schizophrenia	6A20	Preclinical	[7]

60 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[15]
(4-Ethynyl-cyclohex-3-enyl)-dipropyl-amine	DMHQCRU	Discovery agent	N.A.	Investigative	[16]
(4-Phenylethynyl-cyclohex-3-enyl)-dipropyl-amine	DMQM8O5	Discovery agent	N.A.	Investigative	[16]
1-(4-(1H-pyrazol-1-yl)benzyl)-4-phenylpiperazine	DMUDVRM	Discovery agent	N.A.	Investigative	[17]
1-Benzyl-4-(2-ethynyl-pyrrol-1-yl)-piperidine	DMF0GXD	Discovery agent	N.A.	Investigative	[18]
1-Benzyl-4-(2-iodo-pyrrol-1-yl)-piperidine	DMBRJ5S	Discovery agent	N.A.	Investigative	[18]
1-Benzyl-4-(2-oxazol-5-yl-pyrrol-1-yl)-piperidine	DMSBNY8	Discovery agent	N.A.	Investigative	[18]
1-Benzyl-4-(3-oxazol-5-yl-pyrrol-1-yl)-piperidine	DMCJZVA	Discovery agent	N.A.	Investigative	[18]
1-Benzyl-4-pyrrol-1-yl-piperidine	DMNWEC9	Discovery agent	N.A.	Investigative	[18]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine	DMOL2Y0	Discovery agent	N.A.	Investigative	[19]
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]
3-(2-Benzylamino-ethoxy)-phenol	DMZCTGF	Discovery agent	N.A.	Investigative	[20]
3-(4-Methyl-piperidin-1-ylmethyl)-1H-indole	DM0HYDZ	Discovery agent	N.A.	Investigative	[21]
3-(4-Phenyl-piperazin-1-ylmethyl)-1H-indole	DM17SNR	Discovery agent	N.A.	Investigative	[21]
3-(4-Phenyl-piperidin-1-ylmethyl)-1H-indole	DMM0WGI	Discovery agent	N.A.	Investigative	[21]
4-(2-Benzylamino-ethoxy)-1,3-dihydro-indol-2-one	DMYVD2E	Discovery agent	N.A.	Investigative	[20]
4-(4-Benzyl-piperazin-1-yl)-1H-benzoimidazole	DMXAEW9	Discovery agent	N.A.	Investigative	[22]
4-(4-Benzyl-piperazin-1-yl)-1H-indole	DMWR0AS	Discovery agent	N.A.	Investigative	[22]
4-(4-Benzyl-piperazin-1-yl)-5-chloro-1H-indole	DMZ4237	Discovery agent	N.A.	Investigative	[22]
4-(4-Benzyl-piperazin-1-yl)-7-bromo-1H-indole	DMVAB7U	Discovery agent	N.A.	Investigative	[22]
4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine	DM08CG7	Discovery agent	N.A.	Investigative	[1]
A-381393	DMI4TVB	Discovery agent	N.A.	Investigative	[4], [5]
A-425444	DMM5XD6	Discovery agent	N.A.	Investigative	[23]
A412997	DMKY9G5	Discovery agent	N.A.	Investigative	[24]
ABT-670	DM6J57N	Discovery agent	N.A.	Investigative	[23]
Benzyl-[2-(1H-indazol-4-yloxy)-ethyl]-amine	DMTC4G0	Discovery agent	N.A.	Investigative	[20]
Benzyl-[2-(1H-indol-4-yloxy)-ethyl]-amine	DMV6DY7	Discovery agent	N.A.	Investigative	[20]
CP-226269	DMGLO2X	Discovery agent	N.A.	Investigative	[25]
E-1455	DMHPFMV	Schizophrenia	6A20	Investigative	[26]
FAUC 113	DMC6J3B	Discovery agent	N.A.	Investigative	[5]
FAUC213	DM1LMFG	Discovery agent	N.A.	Investigative	[25]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[27]
FLUTROLINE	DMUOHVL	Discovery agent	N.A.	Investigative	[28]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[19]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[29]
JL-18	DM0LD3F	Discovery agent	N.A.	Investigative	[30]
L-741626	DMCYQJF	Discovery agent	N.A.	Investigative	[31]
L-741742	DMP75YK	Discovery agent	N.A.	Investigative	[32]
L-750,667	DM2WUKF	Discovery agent	N.A.	Investigative	[33]
ML398	DMA0E2Q	Discovery agent	N.A.	Investigative	[34]
N-(4-Dipropylaminobutyl)-4-biphenylcarboxamide	DMU1ATH	Discovery agent	N.A.	Investigative	[35]
N-(4-Propylaminobutyl)-4-biphenylcarboxamide	DMG9D7A	Discovery agent	N.A.	Investigative	[35]
nafadotride	DM79KLR	Discovery agent	N.A.	Investigative	[33]
PF-592379	DMY93GJ	Discovery agent	N.A.	Investigative	[36]
PG-01037	DM2TP4Q	Discovery agent	N.A.	Investigative	[37]
piribedil	DMNP6QD	Discovery agent	N.A.	Investigative	[38]
QUINPIROLE	DMDNHEP	Discovery agent	N.A.	Investigative	[39]
RBI257	DM9IQXM	Discovery agent	N.A.	Investigative	[25]
Ro 10-4548	DMXT34V	Discovery agent	N.A.	Investigative	[25]
SB-271046	DM5VJAF	Discovery agent	N.A.	Investigative	[40]
STEPHOLIDINE	DMGMXQC	Discovery agent	N.A.	Investigative	[41]
TKP-1002	DMZU4O8	Schizophrenia	6A20	Investigative	[26]
U101958	DM9GOAV	Discovery agent	N.A.	Investigative	[42]
UH-232	DM5K6ZE	Discovery agent	N.A.	Investigative	[43]
[125I]L750667	DMO7VRJ	Discovery agent	N.A.	Investigative	[44]
[2-(1H-Benzoimidazol-4-yloxy)-ethyl]-benzyl-amine	DMSPMHE	Discovery agent	N.A.	Investigative	[20]
[3H]N-methylspiperone	DM5176Y	Discovery agent	N.A.	Investigative	[33]
[3H]spiperone	DMWHEV8	Discovery agent	N.A.	Investigative	[45], [46]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	1.53E-01	0.03	0.1
Schizophrenia	6A20	Superior temporal cortex	7.13E-01	0.08	0.4
Parkinson's disease	8A00.0	Substantia nigra tissue	1.90E-01	0.19	0.76

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