Target Information
Target General Infomation | |||||
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Target ID |
T30985
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Former ID |
TTDS00087
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Target Name |
Histamine H2 receptor
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Gene Name |
HRH2
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Synonyms |
Gastric receptor I; H2R; Histamine receptor 2; HRH2
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Target Type |
Successful
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Disease | Acid-reflux disorders [ICD9: 530.81; ICD10: K21] | ||||
Duodenal ulcers [ICD10: K25-K27] | |||||
Gastroesophageal reflux disease [ICD9: 140-229, 530; ICD10: K21] | |||||
Gastric ulcer [ICD9: 531; ICD10: K25] | |||||
Gastric secretory disorders [ICD9: 536.8; ICD10: K30] | |||||
Peptic ulcer [ICD9: 531-534; ICD10: K25-K27] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Stomach ulcer [ICD10: K25-K27] | |||||
Ulcerative colitis [ICD9: 556; ICD10: K51] | |||||
Function |
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T30985
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UniProt ID | |||||
Sequence |
MAPNGTASSFCLDSTACKITITVVLAVLILITVAGNVVVCLAVGLNRRLRNLTNCFIVSL
AITDLLLGLLVLPFSAIYQLSCKWSFGKVFCNIYTSLDVMLCTASILNLFMISLDRYCAV MDPLRYPVLVTPVRVAISLVLIWVISITLSFLSIHLGWNSRNETSKGNHTTSKCKVQVNE VYGLVDGLVTFYLPLLIMCITYYRIFKVARDQAKRINHISSWKAATIREHKATVTLAAVM GAFIICWFPYFTAFVYRGLRGDDAINEVLEAIVLWLGYANSALNPILYAALNRDFRTGYQ QLFCCRLANRNSHKTSLRSNASQLSRTQSREPRQQEEKPLKLQVWSGTEVTAPQGATDR |
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Drugs and Mode of Action | |||||
Drug(s) | Betazole | Drug Info | Approved | Gastric secretory disorders | [1], [2] |
Cimetidine | Drug Info | Approved | Acid-reflux disorders | [3], [4] | |
Famotidine | Drug Info | Approved | Peptic ulcer | [5], [6] | |
Nizatidine | Drug Info | Approved | Acid-reflux disorders | [7], [8] | |
Ranitidine | Drug Info | Approved | Peptic ulcer | [5], [9] | |
Ebrotidine | Drug Info | Withdrawn from market | Duodenal ulcers | [10] | |
KU-1257 | Drug Info | Discontinued in Phase 3 | Duodenal ulcers | [11] | |
Osutidine | Drug Info | Discontinued in Phase 3 | Duodenal ulcers | [12] | |
Pibutidine | Drug Info | Discontinued in Phase 3 | Ulcerative colitis | [13] | |
IGN-2098 | Drug Info | Discontinued in Phase 2 | Duodenal ulcers | [14] | |
Lavoltidine | Drug Info | Discontinued in Phase 2 | Gastroesophageal reflux disease | [15] | |
CP-66948 | Drug Info | Discontinued in Phase 1 | Gastric ulcer | [16] | |
TRM-115 | Drug Info | Discontinued in Phase 1 | Gastric ulcer | [17] | |
Z-300 | Drug Info | Discontinued in Phase 1 | Gastric ulcer | [18] | |
CP-331 | Drug Info | Terminated | Pain | [19] | |
FRG-8701 | Drug Info | Terminated | Stomach ulcer | [20] | |
Inhibitor | (+/-)-nantenine | Drug Info | [21] | ||
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [22] | |||
VUF-10148 | Drug Info | [23] | |||
WAY-207024 | Drug Info | [24] | |||
Agonist | amthamine | Drug Info | [25] | ||
arpromidine | Drug Info | [26] | |||
burimamide | Drug Info | [27] | |||
Dimaprit | Drug Info | [28] | |||
impromidine | Drug Info | [26] | |||
oxo-arpromidine | Drug Info | [26] | |||
UR-PG146 | Drug Info | [26] | |||
Antagonist | Betazole | Drug Info | [29] | ||
Cimetidine | Drug Info | [30], [31], [32] | |||
CP-66948 | Drug Info | [33], [28] | |||
Famotidine | Drug Info | [34], [30], [35], [36], [32] | |||
Gaster | Drug Info | [37], [38] | |||
IGN-2098 | Drug Info | [39] | |||
iodoaminopotentidine | Drug Info | [40] | |||
KU-1257 | Drug Info | [41] | |||
Lavoltidine | Drug Info | [42] | |||
Metiamide | Drug Info | [43] | |||
Nizatidine | Drug Info | [44] | |||
Osutidine | Drug Info | [45] | |||
Ranitidine | Drug Info | [46], [37], [32] | |||
tiotidine | Drug Info | [40] | |||
TRM-115 | Drug Info | [47] | |||
Z-300 | Drug Info | [48], [28] | |||
[125I]iodoaminopotentidine | Drug Info | [49] | |||
[3H]tiotidine | Drug Info | [50] | |||
Modulator | CP-331 | Drug Info | [51] | ||
Ebrotidine | Drug Info | [52] | |||
FRG-8701 | Drug Info | [20] | |||
Pibutidine | Drug Info | [53] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Calcium signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
Gastric acid secretion | |||||
PANTHER Pathway | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | ||||
Histamine H2 receptor mediated signaling pathway | |||||
PathWhiz Pathway | Intracellular Signalling Through Histamine H2 Receptor and Histamine | ||||
Gastric Acid Production | |||||
Reactome | Histamine receptors | ||||
G alpha (s) signalling events | |||||
WikiPathways | Monoamine GPCRs | ||||
GPCRs, Class A Rhodopsin-like | |||||
Secretion of Hydrochloric Acid in Parietal Cells | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
REF 1 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7126). | ||||
REF 2 | Drug information of Betazole, 2008. eduDrugs. | ||||
REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 074151. | ||||
REF 4 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1231). | ||||
REF 5 | Clinical review of histamine2 receptor antagonists. Arch Intern Med. 1990 Apr;150(4):745-51. | ||||
REF 6 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7074). | ||||
REF 7 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075616. | ||||
REF 8 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7248). | ||||
REF 9 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1234). | ||||
REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001139) | ||||
REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001852) | ||||
REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002012) | ||||
REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000641) | ||||
REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001447) | ||||
REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000092) | ||||
REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001137) | ||||
REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002138) | ||||
REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001448) | ||||
REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001767) | ||||
REF 20 | Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by necrotizing agents and experimental gastric or duodenal ulcer in rats. Jpn J Pharmacol. 1990 Nov;54(3):277-85. | ||||
REF 21 | Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. | ||||
REF 22 | J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. | ||||
REF 23 | J Med Chem. 2008 Apr 24;51(8):2457-67. Epub 2008 Mar 22.Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo. | ||||
REF 24 | J Med Chem. 2009 Apr 9;52(7):2148-52.Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the gonadotropin releasing hormone receptor (GnRH-R). | ||||
REF 25 | N(G)-acylated aminothiazolylpropylguanidines as potent and selective histamine H(2) receptor agonists. ChemMedChem. 2009 Feb;4(2):232-40. | ||||
REF 26 | Probing ligand-specific histamine H1- and H2-receptor conformations with NG-acylated Imidazolylpropylguanidines. J Pharmacol Exp Ther. 2006 Apr;317(1):139-46. Epub 2006 Jan 4. | ||||
REF 27 | Constitutive activity and structural instability of the wild-type human H2 receptor. J Neurochem. 1998 Aug;71(2):799-807. | ||||
REF 28 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
REF 29 | Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin. Am J Gastroenterol. 1988 Jan;83(1):32-6. | ||||
REF 30 | Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment. J Invest Dermatol. 2001 Feb;116(2):261-5. | ||||
REF 31 | Characterization and modulation of antigen-induced effects in isolated rat heart. J Cardiovasc Pharmacol. 1991 Oct;18(4):556-65. | ||||
REF 32 | Effect of the H2 histamine receptor antagonist on oxygen metabolism in some morphotic blood elements in patients with ulcer disease. Hepatogastroenterology. 1998 Jan-Feb;45(19):276-80. | ||||
REF 33 | CP-66,948: an antisecretory histamine H2-receptor antagonist with mucosal protective properties. Dig Dis Sci. 1991 Dec;36(12):1721-8. | ||||
REF 34 | Blastocyst H(2) receptor is the target for uterine histamine in implantation in the mouse. Development. 2000 Jun;127(12):2643-51. | ||||
REF 35 | Analysis of Vancomycin in the Hindlimb Vascular Bed of the Rat. Am J Ther. 1996 Oct;3(10):681-687. | ||||
REF 36 | Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists. Eur J Clin Invest. 1989 Feb;19(1):1-10. | ||||
REF 37 | Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51. | ||||
REF 38 | Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine. BMC Gastroenterol. 2009 Jun 2;9:40. | ||||
REF 39 | Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric secretion and gastric and duodenal lesions induced in rats. Comparison with roxatidine. Nihon Yakurigaku Zasshi. 1992 Mar;99(3):167-80. | ||||
REF 40 | Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells. Br J Pharmacol. 1997 Nov;122(5):867-74. | ||||
REF 41 | Pharmacological profiles of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy] propyl] urea. Arzneimittelforschung. 1993 Feb;43(2):129-33. | ||||
REF 42 | New and Future Drug Development for Gastroesophageal Reflux Disease. J Neurogastroenterol Motil. 2014 January; 20(1): 6-16. | ||||
REF 43 | Metiamide—an orally active histamine H2-receptor antagonist. 1973. Agents Actions. 1994 Dec;43(3-4):91-5; discussion 96. | ||||
REF 44 | Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy? J Gastrointest Surg. 2009 Mar;13(3):432-7. Epub 2008 Nov 1. | ||||
REF 45 | Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats. Arzneimittelforschung. 2001 Jan;51(1):46-50. | ||||
REF 46 | Hemodynamic significance of histamine synthesis and histamine H1- and H2-receptor gene expression during endotoxemia. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):513-21. Epub 2002 Oct 29. | ||||
REF 47 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002138) | ||||
REF 48 | Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine. Jpn J Pharmacol. 1992 Jul;59(3):275-89. | ||||
REF 49 | G proteins of the Gq family couple the H2 histamine receptor to phospholipase C. Mol Endocrinol. 1996 Dec;10(12):1697-707. | ||||
REF 50 | Tiotidine, a histamine H2 receptor inverse agonist that binds with high affinity to an inactive G-protein-coupled form of the receptor. Experimental support for the cubic ternary complex model. Mol Pharmacol. 2003 Aug;64(2):512-20. | ||||
REF 51 | Conjugation of chlorin p(6) to histamine enhances its cellular uptake and phototoxicity in oral cancer cells. Cancer Chemother Pharmacol. 2011 Aug;68(2):359-69. | ||||
REF 52 | Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat. Arzneimittelforschung. 1997 Apr;47(4A):439-46. | ||||
REF 53 | Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. Mol Pharmacol. 1995 Oct;48(4):774-82. |
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