Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T26500
|
||||
Former ID |
TTDR01193
|
||||
Target Name |
Histamine H4 receptor
|
||||
Gene Name |
HRH4
|
||||
Synonyms |
AXOR35; G protein-coupled receptor 105; GPCR105; GPRv53; H4 receptor; HH4R; SP9144; HRH4
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Asthma [ICD10: J45] | ||||
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4] | |||||
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Function |
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
|
||||
BioChemical Class |
GPCR rhodopsin
|
||||
Target Validation |
T26500
|
||||
UniProt ID | |||||
Sequence |
MPDTNSTINLSLSTRVTLAFFMSLVAFAIMLGNALVILAFVVDKNLRHRSSYFFLNLAIS
DFFVGVISIPLYIPHTLFEWDFGKEICVFWLTTDYLLCTASVYNIVLISYDRYLSVSNAV SYRTQHTGVLKIVTLMVAVWVLAFLVNGPMILVSESWKDEGSECEPGFFSEWYILAITSF LEFVIPVILVAYFNMNIYWSLWKRDHLSRCQSHPGLTAVSSNICGHSFRGRLSSRRSLSA STEVPASFHSERQRRKSSLMFSSRTKMNSNTIASKMGSFSQSDSVALHQREHVELLRARR LAKSLAILLGVFAVCWAPYSLFTIVLSFYSSATGPKSVWYRIAFWLQWFNSFVNPLLYPL CHKRFQKAFLKIFCIKKQPLPSQHSRSVSS |
||||
Drugs and Mode of Action | |||||
Inhibitor | (1H-indol-2-yl)(piperazin-1-yl)methanone | Drug Info | [527934] | ||
(R)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate | Drug Info | [530465] | |||
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole | Drug Info | [551227] | |||
6-(4-Methylpiperazin-1-yl)-9H-purin-2-amine | Drug Info | [530400] | |||
6-(4-methylpiperazin-1-yl)-9Hpurine | Drug Info | [530400] | |||
6-(4-Methylpiperazin-1-yl)pyrimidine-2,4-diamine | Drug Info | [530400] | |||
9-benzyl-6-(4-methylpiperazin-1-yl)-9H-purine | Drug Info | [530400] | |||
A-846714 | Drug Info | [529717] | |||
A-943931 | Drug Info | [529717] | |||
IODOPHENPROPIT | Drug Info | [529455] | |||
JNJ-7777120 | Drug Info | [530796] | |||
Agonist | (S)-alpha-methylhistamine | Drug Info | [525968] | ||
2-(3-bromophenyl)histamine | Drug Info | [527589] | |||
2-methylhistamine | Drug Info | [527985] | |||
4-methylhistamine | Drug Info | [527985] | |||
Clobenpropit | Drug Info | [537147], [537280] | |||
HTMT | Drug Info | [525965] | |||
Imetit | Drug Info | [535960], [536161] | |||
improgan | Drug Info | [525965] | |||
impromidine | Drug Info | [527589] | |||
N,N-dimethylhistamine | Drug Info | [527985] | |||
N-alpha-methyl histamine | Drug Info | [535847] | |||
N-ethylhistamine | Drug Info | [527985] | |||
N-methylhistamine | Drug Info | [526144] | |||
N-[3H]methylhistamine | Drug Info | [535111] | |||
UR-60427 | Drug Info | [543678] | |||
VUF 8430 | Drug Info | [528567] | |||
[3H](R)-alpha-methylhistamine | Drug Info | [535111] | |||
Antagonist | burimamide | Drug Info | [526144] | ||
JNJ-10191584 | Drug Info | [527227] | |||
JNJ-38518168 | Drug Info | [544472] | |||
PF-3893787 | Drug Info | [531625] | |||
Thioperamide | Drug Info | [536039], [536681], [536849] | |||
UR-63325 | Drug Info | [531749] | |||
[3H]JNJ 7777120 | Drug Info | [526927] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Neuroactive ligand-receptor interaction | ||||
Reactome | Histamine receptors | ||||
G alpha (i) signalling events | |||||
WikiPathways | GPCR ligand binding | ||||
GPCR downstream signaling | |||||
GPCRs, Other | |||||
References | |||||
Ref 523293 | ClinicalTrials.gov (NCT01260753) Proof of Activity Study of UR-63325 in Allergic Rhinitis Induced by Nasal Challenge. U.S. National Institutes of Health. | ||||
Ref 525005 | ClinicalTrials.gov (NCT02295865) A Study to Evaluate Safety and Efficacy of Toreforant (JNJ-38518168) in Participants With Moderate to Severe Plaque-type Psoriasis. U.S. National Institutes of Health. | ||||
Ref 531625 | Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602. | ||||
Ref 525965 | Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Mol Pharmacol. 2001 Mar;59(3):434-41. | ||||
Ref 525968 | Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther. 2001 Mar;296(3):1058-66. | ||||
Ref 526144 | Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther. 2001 Oct;299(1):121-30. | ||||
Ref 526927 | A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther. 2004 Apr;309(1):404-13. Epub 2004 Jan 13. | ||||
Ref 527227 | Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5251-6. | ||||
Ref 527589 | Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21. Epub 2005 Jun 9. | ||||
Ref 527934 | J Med Chem. 2005 Dec 29;48(26):8289-98.Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists. | ||||
Ref 527985 | Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives. Br J Pharmacol. 2006 Apr;147(7):744-54. | ||||
Ref 528567 | Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist. J Med Chem. 2006 Nov 16;49(23):6650-1. | ||||
Ref 529455 | J Med Chem. 2008 Jun 12;51(11):3145-53. Epub 2008 May 7.Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. | ||||
Ref 529717 | J Med Chem. 2008 Oct 23;51(20):6547-57. Epub 2008 Sep 26.Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models. | ||||
Ref 530400 | Bioorg Med Chem. 2009 Oct 15;17(20):7186-96. Epub 2009 Sep 2.2,4-Diaminopyrimidines as histamine H4 receptor ligands--Scaffold optimization and pharmacological characterization. | ||||
Ref 530465 | Bioorg Med Chem Lett. 2009 Dec 1;19(23):6682-5. Epub 2009 Oct 6.Histamine H3 and H4 receptor affinity of branched 3-(1H-imidazol-4-yl)propyl N-alkylcarbamates. | ||||
Ref 530796 | Bioorg Med Chem Lett. 2010 Apr 15;20(8):2516-9. Epub 2010 Mar 3.Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists. | ||||
Ref 531625 | Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602. | ||||
Ref 531749 | Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012 Jan 1;4:967-87. | ||||
Ref 535111 | Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6. | ||||
Ref 535847 | Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol. 2003 Nov;140(6):1117-27. Epub 2003 Oct 6. | ||||
Ref 535960 | Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol. 2004 May;142(1):161-71. | ||||
Ref 536039 | The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20. | ||||
Ref 536161 | Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors. J Neurophysiol. 2006 Apr;95(4):2492-500. Epub 2005 Dec 14. | ||||
Ref 536681 | Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury. Neuroimmunomodulation. 2007;14(6):317-25. Epub 2008 Apr 10. | ||||
Ref 536849 | Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain. J Neurochem. 2008 Nov;107(4):976-86. Epub 2008 Sep 11. | ||||
Ref 537147 | The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol. 2009 Mar;123(3):619-25. | ||||
Ref 537280 | Clobenpropit analogs as dual activity ligands for the histamine H3 and H4 receptors: synthesis, pharmacological evaluation, and cross-target QSAR studies. Bioorg Med Chem. 2009 Jun 1;17(11):3987-94. Epub 2009 Apr 11. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.