Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT07C3Y)

• DTT Name: 5-HT 4 receptor (HTR4)
• Synonyms: Serotonin receptor 4; 5-hydroxytryptamine receptor 4; 5-HT4 receptor; 5-HT4; 5-HT-4
• Gene Name: HTR4
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: 5HT4R_HUMAN
• TTD ID: T59679
• Sequence:
  MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV
  SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY
  AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN
  STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP
  QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL
  GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD
  AVECGGQWESQCHPPATSPLVAAQPSDT
• Function: The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Serotonin receptors (R-HSA-390666)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisapride	DMY7PED	Gastroesophageal reflux disease	DA22.Z	Approved	[1]
HTF 919	DM78G6F	Constipation	DD91.1	Approved	[2]
R0-93877	DMM4U9G	Constipation	DD91.1	Approved	[3]
Tegaserod	DM3XYD1	Irritable bowel syndrome	DD91.0	Approved	[4]
Mosapride	DM2VOQ3	N. A.	N. A.	Phase 4	[5]

17 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Renzapride	DM7HQNX	Irritable bowel syndrome	DD91.0	Phase 3	[6]
DSP-6952	DM6UGHA	Constipation	DD91.1	Phase 2	[7]
Lintopride	DMSHGWN	Nausea	MD90	Phase 2	[8]
PF-885706	DM0KRLJ	Gastroesophageal reflux disease	DA22.Z	Phase 2	[9]
Piboserod	DM3ZEYL	Atrial fibrillation	BC81.3	Phase 2	[3]
PRX-3140	DMEVXS1	Alzheimer disease	8A20	Phase 2	[10]
SB-207266A	DM27KFY	Irritable bowel syndrome	DD91.0	Phase 2	[3]
SPD-557	DMJH2AC	Diabetic gastroparesis	DA41.00	Phase 2	[11]
TD-5108	DM6SANW	Gastroparesis	DA41.00	Phase 2	[5]
TD-8954	DM3C9NV	Gastrointestinal disease	DE2Z	Phase 2	[12]
YKP-GI	DM740LV	Constipation	DD91.1	Phase 2	[13]
BIMU-1	DMBTSZD	Cognitive impairment	6D71	Phase 1	[14]
DA-6886	DMKPAOD	Irritable bowel syndrome	DD91.0	Phase 1	[11]
M-0004	DMK7UNL	Gastroesophageal reflux disease	DA22.Z	Phase 1	[11]
PF-04995274	DMZ8QRI	Alzheimer disease	8A20	Phase 1	[15]
SER-101	DMTZ983	Congestive heart failure	BD10	Phase 1	[16]
SUVN-D4010	DM6ZOD2	Alzheimer disease	8A20	Phase 1	[17]

11 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E-3620	DMWF95G	Gastric motility disorder	DA21	Discontinued in Phase 2	[18]
Fabesetron	DMMSFK0	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[19]
Naronapride	DM8BHL6	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[20]
Norcisapride	DMJSKUI	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[21]
SL65.0155	DMAM9BD	Parkinson disease	8A00.0	Discontinued in Phase 2	[22]
TD-2749	DMCA97F	Gastrointestinal disease	DE2Z	Discontinued in Phase 1	[23]
DAU-6285	DMP9GFZ	Vomiting	MD90	Terminated	[24]
LY-353433	DMFVYID	Inflammatory bowel disease	DD72	Terminated	[25]
SB 203186	DMNJ7LY	N. A.	N. A.	Terminated	[2]
SC-53116	DM2O8SF	Gastric motility disorder	DA21	Terminated	[26]
SK-951	DM6RVXU	Gastrointestinal disease	DE2Z	Terminated	[27]

30 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-zacopride	DMT6J51	Discovery agent	N.A.	Investigative	[28]
1-((S)-2-aminopropyl)-1H-indazol-6-ol	DMU83KP	Discovery agent	N.A.	Investigative	[29]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[30]
AF-3473	DM6B9CK	Neuropathic pain	8E43.0	Investigative	[11]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[31]
BARETTIN	DMU3D2O	Discovery agent	N.A.	Investigative	[32]
ER-21018	DMUNO4R	Gastrointestinal disease	DE2Z	Investigative	[11]
GR 125487	DM72B86	Discovery agent	N.A.	Investigative	[33]
GR-113808	DMFU9VH	Discovery agent	N.A.	Investigative	[34]
MDDR 287569	DMZJPOB	Urinary incontinence	MF50.2	Investigative	[35]
ML 10375	DM4ZNOU	Discovery agent	N.A.	Investigative	[36]
ML-10302	DMM5P8Q	Discovery agent	N.A.	Investigative	[37]
R-116712	DMJ14OV	Pain	MG30-MG3Z	Investigative	[38]
RO 116 1148	DMMO6PH	Discovery agent	N.A.	Investigative	[39]
RQ-00000010	DMLN280	Gastric motility disorder	DA21	Investigative	[11]
RS 100235	DM32ZIC	Discovery agent	N.A.	Investigative	[40]
RS 116 0086	DMX9W0T	Discovery agent	N.A.	Investigative	[39]
RS 57639	DMD91WS	Discovery agent	N.A.	Investigative	[31]
RS 67333	DMO7G94	Discovery agent	N.A.	Investigative	[41]
RS67506	DM89I0L	Discovery agent	N.A.	Investigative	[42]
SB 204070	DM43K85	Discovery agent	N.A.	Investigative	[31]
SB-207710	DMVQKMC	Discovery agent	N.A.	Investigative	[43]
SC-52491	DMJ576C	Discovery agent	N.A.	Investigative	[44]
SC-54750	DMEUTXG	Discovery agent	N.A.	Investigative	[44]
SDZ-205-557	DMP3EXG	Discovery agent	N.A.	Investigative	[45]
SEROTONIN	DMOFCRY	Discovery agent	N.A.	Investigative	[32]
SUVN-1004028	DMQ5GMV	Neurodegenerative disorder	8A20-8A23	Investigative	[11]
VRX-03011	DMCXZGU	Discovery agent	N.A.	Investigative	[46]
[11C]SB207145	DMOZ8E3	Discovery agent	N.A.	Investigative	[47]
[123I]SB 207710	DMMG1TA	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	3.29E-01	-0.04	-0.05
Schizophrenia	6A20	Superior temporal cortex	4.25E-01	0.03	0.13
Parkinson's disease	8A00.0	Substantia nigra tissue	6.16E-01	-0.03	-0.24
Alzheimer's disease	8A00.0	Entorhinal cortex	1.70E-02	-0.17	-0.32
Irritable bowel syndrome	DD91.0	Rectal colon tissue	5.87E-01	1.36E-02	0.06

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