Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0K1SC)

• DTT Name: 5-HT 2B receptor (HTR2B)
• Synonyms: Serotonin receptor 2B; 5-hydroxytryptamine receptor 2B; 5-HT2B; 5-HT-2B; 5-HT 2B
• Gene Name: HTR2B
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: 5HT2B_HUMAN
• TTD ID: T31204
• Sequence:
  MALSYRVSELQSTIPEHILQSTFVHVISSNWSGLQTESIPEEMKQIVEEQGNKLHWAALL
  ILMVIIPTIGGNTLVILAVSLEKKLQYATNYFLMSLAVADLLVGLFVMPIALLTIMFEAM
  WPLPLVLCPAWLFLDVLFSTASIMHLCAISVDRYIAIKKPIQANQYNSRATAFIKITVVW
  LISIGIAIPVPIKGIETDVDNPNNITCVLTKERFGDFMLFGSLAAFFTPLAIMIVTYFLT
  IHALQKKAYLVKNKPPQRLTWLTVSTVFQRDETPCSSPEKVAMLDGSRKDKALPNSGDET
  LMRRTSTIGKKSVQTISNEQRASKVLGIVFFLFLLMWCPFFITNITLVLCDSCNQTTLQM
  LLEIFVWIGYVSSGVNPLVYTLFNKTFRDAFGRYITCNYRATKSVKTLRKRSSKIYFRNP
  MAENSKFFKKHGIRNGINPAMYQSPMRLRSSTIQSSSIILLDTLLLTENEGDKTEEQVSY
  V
• Function: Functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine. G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Gap junction (hsa04540)
  Serotonergic synapse (hsa04726)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Serotonin receptors (R-HSA-390666)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[2]
Minaprine	DM0EP7M	Depression	6A70-6A7Z	Approved	[3]
Triflupromazine	DMKFQJP	Nausea	MD90	Approved	[1]
SPN-812	DMTV7XH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[4]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PRX-08066	DMR7H2V	Pulmonary arterial hypertension	BB01.0	Phase 2	[5]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[6]

9 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pyrazole-3-carboxamide derivative 1	DMVQXZJ	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 23	DM5MLQU	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 24	DMOQ726	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 25	DM51MFS	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 26	DM90WKN	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 27	DMIQSDW	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 28	DM1D2AS	N. A.	N. A.	Patented	[7]
Pyrimidine derivative 29	DMVOYJ8	N. A.	N. A.	Patented	[7]
Quinoline derivative 2	DMNO2BP	N. A.	N. A.	Patented	[7]

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FENDILINE	DMH6NG5	Coronary artery disease	BA80	Withdrawn from market	[8]
Ritanserin	DM0X36Y	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[9]
MT-500	DMCJ1B2	Migraine	8A80	Discontinued in Phase 1	[10]
LY53857	DMY71LJ	N. A.	N. A.	Terminated	[9]
Ro-60-0175	DMZSQU8	N. A.	N. A.	Terminated	[11]
SB 206553	DMS0QEP	N. A.	N. A.	Terminated	[12]

74 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-norfenfluramine	DMOZJA5	Discovery agent	N.A.	Investigative	[13]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[14]
(-)-norfenfluramine	DMOY9J8	Discovery agent	N.A.	Investigative	[13]
(2S)-1-(6-methoxy-1H-indazol-1-yl)propan-2-amine	DMYALON	Discovery agent	N.A.	Investigative	[15]
(5-methoxy-1H-indol-3-yl)methanamine	DMOPMNC	Discovery agent	N.A.	Investigative	[8]
1-((R)-2-aminopropyl)-1H-indazol-6-ol	DM74R0E	Discovery agent	N.A.	Investigative	[15]
1-((S)-2-aminopropyl)-1H-indazol-6-ol	DMU83KP	Discovery agent	N.A.	Investigative	[15]
1-((S)-2-aminopropyl)-7-chloro-1H-indazol-6-ol	DMRFJNC	Discovery agent	N.A.	Investigative	[15]
1-((S)-2-aminopropyl)-7-fluoro-1H-indazol-6-ol	DM76JVB	Discovery agent	N.A.	Investigative	[15]
1-((S)-2-aminopropyl)-7-iodo-1H-indazol-6-ol	DMR2SXL	Discovery agent	N.A.	Investigative	[15]
1-((S)-2-aminopropyl)-7-methyl-1H-indazol-6-ol	DM8MNZG	Discovery agent	N.A.	Investigative	[15]
1-(2-aminoethyl)-1H-indazol-6-ol	DMKWO6A	Discovery agent	N.A.	Investigative	[15]
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine	DMX5N3V	Discovery agent	N.A.	Investigative	[16]
1-Butyl-3-(2-dimethylamino-ethyl)-1H-indol-4-ol	DMO7NXE	Discovery agent	N.A.	Investigative	[17]
1-naphthylpiperazine	DM6BIWK	Discovery agent	N.A.	Investigative	[18]
2-(5-Methoxy-1H-indol-3-yl)-1-methyl-ethylamine	DM1O0JD	Discovery agent	N.A.	Investigative	[15]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[18]
3-(2-Amino-propyl)-1H-indol-5-ol	DMQPNUM	Discovery agent	N.A.	Investigative	[15]
3-(2-Dimethylamino-ethyl)-1-methyl-1H-indol-4-ol	DMKYZGD	Discovery agent	N.A.	Investigative	[17]
3-(2-Dimethylamino-ethyl)-1H-indol-6-ol	DM32MIE	Discovery agent	N.A.	Investigative	[17]
3-(2-Dimethylamino-propyl)-1H-indol-4-ol	DMMJP9D	Discovery agent	N.A.	Investigative	[17]
3-(2-Pyrrolidin-1-yl-ethyl)-1H-indol-4-ol	DM7VJPX	Discovery agent	N.A.	Investigative	[17]
3-(3-Dimethylamino-propyl)-1H-indol-4-ol	DM0O2ZB	Discovery agent	N.A.	Investigative	[17]
3-Dimethylaminomethyl-1-methyl-1H-indol-4-ol	DMDOIJM	Discovery agent	N.A.	Investigative	[17]
3-Dimethylaminomethyl-1H-indol-4-ol	DMSJUOH	Discovery agent	N.A.	Investigative	[17]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[19]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[18]
5-MEO-DMT	DMG0EL7	Discovery agent	N.A.	Investigative	[15]
6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine	DM592FB	Discovery agent	N.A.	Investigative	[20]
6-Fluoromelatonin	DMKFUO0	Discovery agent	N.A.	Investigative	[8]
7,8,9,10-tetrahydro-6H-furo-[2,3-g][3]benzazepine	DMIMLUO	Discovery agent	N.A.	Investigative	[20]
7,8,9,10-tetrahydro-6H-furo-[3,2-g][3]benzazepine	DMVZA27	Discovery agent	N.A.	Investigative	[20]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[21]
ADRENOGLOMERULOTROPIN	DMP8NSU	Discovery agent	N.A.	Investigative	[8]
ADS-103253	DMH9A4S	Discovery agent	N.A.	Investigative	[22]
ADS-103274	DMBN6IE	Discovery agent	N.A.	Investigative	[22]
AL-37350A	DMRJ2GK	Discovery agent	N.A.	Investigative	[23]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[24]
BRL-15572	DMM61Y2	Discovery agent	N.A.	Investigative	[25]
BW723C86	DME15JU	Discovery agent	N.A.	Investigative	[26]
CHLOROPHENYLPIPERAZINE	DMOA8L2	Discovery agent	N.A.	Investigative	[27]
dihydroergocryptine	DMDW2NL	Discovery agent	N.A.	Investigative	[28]
EGIS-7625	DMLK4X5	Discovery agent	N.A.	Investigative	[29]
LY86057	DM5TYMG	Discovery agent	N.A.	Investigative	[18]
m-chlorophenylpiperazine	DMM1J2D	Discovery agent	N.A.	Investigative	[18]
METHYLENEDIOXYMETHAMPHETAMINE	DMYVU47	Discovery agent	N.A.	Investigative	[30]
norfenfluramine	DMGI4ZW	Discovery agent	N.A.	Investigative	[13]
norfluoxetine	DMKNUP3	Discovery agent	N.A.	Investigative	[13]
Org 12962	DM8JUBG	Discovery agent	N.A.	Investigative	[2]
piribedil	DMNP6QD	Discovery agent	N.A.	Investigative	[31]
R-1	DMK0YP7	Irritable bowel syndrome	DD91.0	Investigative	[32]
Racemic DOI	DM39FSQ	Discovery agent	N.A.	Investigative	[21]
RQ-00310941	DMYK6OU	Irritable bowel syndrome	DD91.0	Investigative	[32]
SB 204741	DM3LQF4	Discovery agent	N.A.	Investigative	[2]
SB 215505	DMCM4LT	Discovery agent	N.A.	Investigative	[33]
SB 216641	DMB3R4Z	Discovery agent	N.A.	Investigative	[25]
SB 221284	DM8DVY2	Discovery agent	N.A.	Investigative	[2]
SB 228357	DMKA8R4	Discovery agent	N.A.	Investigative	[34]
SB 242084	DMISBDC	Discovery agent	N.A.	Investigative	[35]
SEROTONIN	DMOFCRY	Discovery agent	N.A.	Investigative	[11]
spiramide	DM5KNMD	Discovery agent	N.A.	Investigative	[2]
spiroxatrine	DMPHRXQ	Discovery agent	N.A.	Investigative	[36]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[18]
VER-2692	DM5WAM8	Discovery agent	N.A.	Investigative	[11]
VER-3323	DM7O2K1	Discovery agent	N.A.	Investigative	[37]
VER-5384	DMC2EO9	Discovery agent	N.A.	Investigative	[37]
VER-5593	DMZ2V0A	Discovery agent	N.A.	Investigative	[37]
YM-348	DM38F9T	Discovery agent	N.A.	Investigative	[20]
[125I]DOI	DMQUY08	Discovery agent	N.A.	Investigative	[32]
[2-(4-Fluoro-1H-indol-3-yl)-ethyl]-dimethyl-amine	DMDIH96	Discovery agent	N.A.	Investigative	[17]
[3H]5-HT	DMYJXV7	Discovery agent	N.A.	Investigative	[18]
[3H]LSD	DM0YJHS	Discovery agent	N.A.	Investigative	[38]
[3H]mesulergine	DM8K6VF	Discovery agent	N.A.	Investigative	[2]
[3H]rauwolscine	DMBQZ2H	Discovery agent	N.A.	Investigative	[36]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	2.08E-01	-0.05	-0.23
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.58E-01	0.18	0.45
Multiple myeloma	2C82	Bone marrow	2.12E-02	-0.22	-0.9
Schizophrenia	6A20	Pre-frontal cortex	1.29E-01	-0.04	-0.14
Schizophrenia	6A20	Superior temporal cortex	1.13E-01	-0.04	-0.26

References

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