Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Histamine H1 receptor (H1R)
• Synonyms: HH1R; H1R
• Gene Name: HRH1
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: HRH1_HUMAN
• TTD ID: T77913
• Sequence:
  MSLPNSSCLLEDKMCEGNKTTMASPQLMPLVVVLSTICLVTVGLNLLVLYAVRSERKLHT
  VGNLYIVSLSVADLIVGAVVMPMNILYLLMSKWSLGRPLCLFWLSMDYVASTASIFSVFI
  LCIDRYRSVQQPLRYLKYRTKTRASATILGAWFLSFLWVIPILGWNHFMQQTSVRREDKC
  ETDFYDVTWFKVMTAIINFYLPTLLMLWFYAKIYKAVRQHCQHRELINRSLPSFSEIKLR
  PENPKGDAKKPGKESPWEVLKRKPKDAGGGSVLKSPSQTPKEMKSPVVFSQEDDREVDKL
  YCFPLDIVHMQAAAEGSSRDYVAVNRSHGQLKTDEQGLNTHGASEISEDQMLGDSQSFSR
  TDSDTTTETAPGKGKLRSGSNTGLDYIKFTWKRLRSHSRQYVSGLHMNRERKAAKQLGFI
  MAAFILCWIPYFIFFMVIAFCKNCCNEHLHMFTIWLGYINSTLNPLIYPLCNENFKKTFK
  RILHIRS
• Function: In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Histamine receptors (R-HSA-390650)

Molecular Interaction Atlas (MIA) of This DTT

55 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-(+)-Dimethindene maleate	DMMHNU2	Pruritus	EC90	Approved	[2]
Aceprometazine	DM1SRQT	Sleep-wake disorder	7A00-7B2Z	Approved	[3]
Acrivastine	DMTIGA0	Allergic rhinitis	CA08.0	Approved	[4]
Alcaftadine	DM5J1NH	Allergic conjunctivitis	9A60.02	Approved	[5]
Antazoline	DMA04JS	Allergic rhinitis	CA08.0	Approved	[6]
Azatadine	DMZ80SB	Allergic rhinitis	CA08.0	Approved	[7]
Azelastine	DMXTMBJ	Allergic conjunctivitis	9A60.02	Approved	[8]
Bepotastine	DMXDZAQ	Allergic rhinitis	CA08.0	Approved	[9]
Bromodiphenhydramine	DMNDJT5	Common cold	CA00	Approved	[10]
Brompheniramine	DMFOVSD	Allergic rhinitis	CA08.0	Approved	[11]
Buclizine	DMXKZT3	Nausea	MD90	Approved	[12]
Carbinoxamine	DMCT31R	Allergic rhinitis	CA08.0	Approved	[13]
Cetirizine	DMOMP9U	Allergic rhinitis	CA08.0	Approved	[14]
Chlophedianol	DMXGJEI	Allergic rhinitis	CA08.0	Approved	[15]
Chlorpheniramine	DM5URA2	Allergic rhinitis	CA08.0	Approved	[8]
Cinnarizine	DM7U5QJ	Meniere disease	AB31.0	Approved	[16]
Clemastine	DMBZWQL	Allergic rhinitis	CA08.0	Approved	[1]
Cyclizine	DM9G7BS	Allergic rhinitis	CA08.0	Approved	[17]
Cyproheptadine	DM92AH3	Allergic rhinitis	CA08.0	Approved	[18]
Desloratadine	DM56YN7	Allergic rhinitis	CA08.0	Approved	[19]
Dexbrompheniramine	DMKVWGE	Allergic rhinitis	CA08.0	Approved	[20]
Dexchlorpheniramine Maleate	DMA8DPN	Allergic rhinitis	CA08.0	Approved	[21]
Dimenhydrinate	DM264B3	Meniere disease	AB31.0	Approved	[22]
Dimethindene	DM32YAI	Respiratory allergy	4A80	Approved	[2]
Diphenhydramine	DMKQTBA	Hyperemesis gravidarum		Approved	[8]
Diphenylpyraline	DMW4X37	Allergic rhinitis	CA08.0	Approved	[23]
Doxepin	DMPI98T	Anxiety		Approved	[24]
Doxylamine	DMKOXFE	Allergic rhinitis	CA08.0	Approved	[25]
Emedastine	DM36LAJ	Allergic conjunctivitis	9A60.02	Approved	[26]
Epinastine	DMX0K3Q	Allergic conjunctivitis	9A60.02	Approved	[27]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[28]
Ethopropazine	DM0N3L7	Parkinson disease	8A00.0	Approved	[21]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[29]
Hydroxyzine	DMF8Y74	Allergic rhinitis	CA08.0	Approved	[30]
Ketotifen	DM74XKS	Allergic conjunctivitis	9A60.02	Approved	[8]
Levocabastine	DMMZPWT	Allergic conjunctivitis	9A60.02	Approved	[31]
Levocetirizine dihydrochloride	DMW6ZJI	Allergic rhinitis	CA08.0	Approved	[29]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[32]
Mepyramine	DMB4SFH	Allergic rhinitis	CA08.0	Approved	[33]
Mepyramine maleate	DM7F5OW	Allergy	4A80-4A85	Approved	[33]
Mequitazine	DMAFBCY	Allergic rhinitis	CA08.0	Approved	[34]
Methdilazine	DMAUHQX	Allergic rhinitis	CA08.0	Approved	[35]
Mizolastine	DM1FDN8	Allergic rhinitis	CA08.0	Approved	[36]
Olopatadine	DMKMWQG	Allergic conjunctivitis	9A60.02	Approved	[37]
Oxatomide	DM1F42Z	Hay fever	CA08.00	Approved	[8]
Pemirolast	DML97WV	Allergic conjunctivitis	9A60.02	Approved	[38]
Phenindamine	DMDTC7R	Allergic rhinitis	CA08.0	Approved	[39]
Pheniramine	DMCH7RU	Allergic rhinitis	CA08.0	Approved	[40]
Promethazine	DM6I5GR	Hyperemesis gravidarum		Approved	[8]
Propiomazine	DMKY8V1	Insomnia	7A00-7A0Z	Approved	[41]
Tranilast	DME5Y64	Allergic rhinitis	CA08.0	Approved	[37]
Trimeprazine	DMEMV9D	Allergic rhinitis	CA08.0	Approved	[42]
Tripelennamine	DMZBU15	Allergic rhinitis	CA08.0	Approved	[43]
Triprolidine	DM7SWIA	Allergic rhinitis	CA08.0	Approved	[44]
RUPATADINE	DMBPN7T	N. A.	N. A.	Phase 4	[45]

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AC-170	DMXZ9T3	Allergic conjunctivitis	9A60.02	Phase 3	[46]
Carebastine	DMUVMWZ	Ocular allergy	4A81	Phase 3	[37]
E-4716	DMC5PB2	Respiratory disease	CB40	Phase 2	[47]
LY-2624803	DMTPQUA	Insomnia	7A00-7A0Z	Phase 2	[48]
Noberastine	DME8IFQ	Asthma	CA23	Phase 2	[49]
OBE-101	DMJIBSG	Obesity	5B81	Phase 2	[50]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[51]
UCB-35440	DM5Z34K	Rhinitis	FA20	Phase 2	[52]
Vapitadine	DMNFVKC	Allergic skin disorder	4A82	Phase 2	[53]

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Citalopram derivative 1	DMITX1G	N. A.	N. A.	Patented	[54]
Piperidine derivative 1	DMHN5KW	N. A.	N. A.	Patented	[54]
PMID29334795-Compound-61	DM9H3LI	N. A.	N. A.	Patented	[54]

12 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Astemizole	DM2HN6Q	Allergic rhinitis	CA08.0	Withdrawn from market	[55]
Terfenadine	DM4KLPT	Allergy	4A80-4A85	Withdrawn from market	[56]
Norastemizole	DMXF0NS	N. A.	N. A.	Discontinued in Preregistration	[57]
GSK835726	DMRNJPY	Allergic rhinitis	CA08.0	Discontinued in Phase 2	[58]
HSR-609	DM1PJ0V	Rhinitis	FA20	Discontinued in Phase 2	[59]
Mequitamium iodide	DM2DK4A	Asthma	CA23	Discontinued in Phase 2	[60]
ReN-1869	DMHCBQS	Pain	MG30-MG3Z	Discontinued in Phase 2	[61]
SUN-1334H	DMWTLQ4	Allergic rhinitis	CA08.0	Discontinued in Phase 2	[62]
AZD-1744	DMCOMG5	Asthma	CA23	Discontinued in Phase 1	[63]
GSK1004723	DMEC6RD	Allergic rhinitis	CA08.0	Discontinued in Phase 1	[58]
KA-398	DM0MXWC	Asthma	CA23	Terminated	[64]
Selenotifen	DM4ESAP	Asthma	CA23	Terminated	[65]

47 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-cis-H2-PAT	DMDFR59	Discovery agent	N.A.	Investigative	[66]
(+)-trans-H2-PAT	DMAN63P	Discovery agent	N.A.	Investigative	[66]
(+/-)-cis-H2-PAT	DMAHO9M	Discovery agent	N.A.	Investigative	[66]
(-)-trans-H2-PAT	DMITWZ7	Discovery agent	N.A.	Investigative	[66]
(S)-cetirizine	DMJN659	Discovery agent	N.A.	Investigative	[67]
1-(4-p-Tolyl-butyl)-piperidine	DMFYK6T	Discovery agent	N.A.	Investigative	[68]
1-[(Furan-2(5H)-one)-4-methyl]-desloratadine	DMQPFT3	Discovery agent	N.A.	Investigative	[69]
2-(2-thiazolyl)ethanamine	DMRL65E	Discovery agent	N.A.	Investigative	[70]
2-(3-bromophenyl)histamine	DM260RG	Discovery agent	N.A.	Investigative	[70]
2-(3-chlorophenyl)histamine	DMO0Y79	Discovery agent	N.A.	Investigative	[70]
2-(3-iodophenyl)histamine	DMML0VP	Discovery agent	N.A.	Investigative	[70]
2-(9,10-dihydroanthracen-9-yl)-N-methylethanamine	DMRW475	Discovery agent	N.A.	Investigative	[71]
2-pyridylethylamine	DMN516S	Discovery agent	N.A.	Investigative	[67]
3,3-diphenylpropan-1-amine	DMNOUSV	Discovery agent	N.A.	Investigative	[71]
4,4-Diphenylbutan-1-amine	DMQ0TBX	Discovery agent	N.A.	Investigative	[71]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[72]
8R-Lisuride	DMLK4WO	Discovery agent	N.A.	Investigative	[73]
9-(2-aminoethyl)-9,10-dihydroanthracene	DM4Y9U3	Discovery agent	N.A.	Investigative	[71]
9-(2-aminopropyl)-9,10-dihydroanthracene	DMND39P	Discovery agent	N.A.	Investigative	[71]
9-(Aminomethyl)-9,10-dihydroanthracene	DM6QDNH	Discovery agent	N.A.	Investigative	[71]
9-OH-risperidone	DMGORXQ	Discovery agent	N.A.	Investigative	[74]
9-Phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine	DMRCM7Q	Discovery agent	N.A.	Investigative	[75]
arpromidine	DMB9PDA	Discovery agent	N.A.	Investigative	[70]
BU-E 47	DM1D47I	Discovery agent	N.A.	Investigative	[70]
DIMEBOLIN	DMV8ZQG	Discovery agent	N.A.	Investigative	[76]
dimethylhistaprodifen	DMY0FVU	Discovery agent	N.A.	Investigative	[70]
Diphenyl(piperidin-4-yl)methanol	DMO4XUC	Discovery agent	N.A.	Investigative	[68]
histaprodifen	DMA9YIB	Discovery agent	N.A.	Investigative	[77]
Hydroxyclemastine	DM5DOEC	Discovery agent	N.A.	Investigative	[1]
impromidine	DMTDRPM	Discovery agent	N.A.	Investigative	[78]
KF-A6	DMQJ3T5	Discovery agent	N.A.	Investigative	[79]
MDL-28163	DMUHJ2C	Discovery agent	N.A.	Investigative	[45]
methylhistaprodifen	DM7PRDY	Discovery agent	N.A.	Investigative	[70]
N,N-dimethyl-2,2-diphenylethanamine	DMJDQGR	Discovery agent	N.A.	Investigative	[71]
N,N-Dimethyl-3,3-diphenylpropan-1-amine	DMIP5K7	Discovery agent	N.A.	Investigative	[71]
N,N-dimethyl-4,4-diphenylbutan-1-amine	DMX9U7S	Discovery agent	N.A.	Investigative	[71]
N-methyl-3,3-diphenylpropan-1-amine	DM8IHQP	Discovery agent	N.A.	Investigative	[71]
N-methyl-4,4-diphenylbutan-1-amine	DMO3PNF	Discovery agent	N.A.	Investigative	[71]
OCTOCLOTHEPIN	DM0UADK	Discovery agent	N.A.	Investigative	[80]
oxo-arpromidine	DMV0KTW	Discovery agent	N.A.	Investigative	[78]
R-226161	DM4BP7S	Discovery agent	N.A.	Investigative	[81]
R-dimethindene	DM6FVZW	Discovery agent	N.A.	Investigative	[82]
UR-PG131A	DM2C6GB	Discovery agent	N.A.	Investigative	[78]
UR-PG146	DMQCL6Y	Discovery agent	N.A.	Investigative	[78]
UR-PG153	DM3VTLG	Discovery agent	N.A.	Investigative	[78]
UR-PG55B	DM6SM4N	Discovery agent	N.A.	Investigative	[78]
VUF-10148	DM89PMC	Discovery agent	N.A.	Investigative	[83]

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	2.21E-01	-0.17	-0.25
Parkinson's disease	8A00.0	Substantia nigra tissue	6.74E-01	0.13	0.43
Sensitive skin	EA90	Skin	4.04E-01	0.06	0.17
Asthma	CA23	Nasal and bronchial airway	6.86E-09	0.3	0.55

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