Target Information
Target General Infomation | |||||
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Target ID |
T52790
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Former ID |
TTDC00090
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Target Name |
NK-2 receptor
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Gene Name |
TACR2
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Synonyms |
NK-2 receptor; NK-2R; Neurokinin A receptor; SKR; Tachykinin neurokinin 2 receptor; Tachykinin receptor 2; TACR2
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Target Type |
Clinical Trial
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Disease | Asthma [ICD10: J45] | ||||
Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42] | |||||
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47] | |||||
Depression; Anxiety [ICD9: 300, 311; ICD10: F30-F39, F40-F42] | |||||
Depression; Acute or chronic pain; Anxiety disorders; Urinary incontinence [ICD9: 300, 311, 338, 338.2, 787.6, 788.3,780; ICD10: F30-F42, N39.3-N39.4, G89] | |||||
Infantile colics; Postoperative ileus [ICD9: 537.2, 560.1, 560.31, 777.1, 777.4, 789.7; ICD10: K31.5, K56.0, K56.3, K56.7, P76.1, R10.4] | |||||
Irritable bowel syndrome [ICD9: 564.1, 787.91; ICD10: A09, K58, K59.1] | |||||
Irritable bowel syndrome with diarrhoea [ICD9: 493, 564.1, 787.91; ICD10: A09, J45, K58, K59.1] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Urinary incontinence [ICD9: 788.3; ICD10: N39.3, N39.4, R32] | |||||
Unspecified [ICD code not available] | |||||
Function |
This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T52790
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UniProt ID | |||||
Sequence |
MGTCDIVTEANISSGPESNTTGITAFSMPSWQLALWATAYLALVLVAVTGNAIVIWIILA
HRRMRTVTNYFIVNLALADLCMAAFNAAFNFVYASHNIWYFGRAFCYFQNLFPITAMFVS IYSMTAIAADRYMAIVHPFQPRLSAPSTKAVIAGIWLVALALASPQCFYSTVTMDQGATK CVVAWPEDSGGKTLLLYHLVVIALIYFLPLAVMFVAYSVIGLTLWRRAVPGHQAHGANLR HLQAMKKFVKTMVLVVLTFAICWLPYHLYFILGSFQEDIYCHKFIQQVYLALFWLAMSST MYNPIIYCCLNHRFRSGFRLAFRCCPWVTPTKEDKLELTPTTSLSTRVNRCHTKETLFMA GDTAPSEATSGEAGRPQDGSGLWFGYGLLAPTKTHVEI |
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Drugs and Mode of Action | |||||
Drug(s) | Ibodutant | Drug Info | Phase 3 | Irritable bowel syndrome | [1], [2] |
Nepadutant | Drug Info | Phase 1/2 | Infantile colics; Postoperative ileus | [3], [4] | |
SLV-332 | Drug Info | Preclinical | Irritable bowel syndrome | [5] | |
Saredutant | Drug Info | Discontinued in Phase 3 | Depression; Anxiety | [6], [7] | |
CS-003 | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [8] | |
DNK-333 | Drug Info | Discontinued in Phase 2 | Irritable bowel syndrome with diarrhoea | [8] | |
FK-224 | Drug Info | Discontinued in Phase 2 | Asthma | [9], [10] | |
AVE-5883 | Drug Info | Discontinued in Phase 1/2 | Asthma | [11] | |
SR 144190 | Drug Info | Discontinued in Phase 1 | Depression; Acute or chronic pain; Anxiety disorders; Urinary incontinence | [12] | |
UK-224671 | Drug Info | Discontinued in Phase 1 | Urinary incontinence | [13] | |
AZD-5106 | Drug Info | Terminated | Urinary incontinence | [14] | |
GR-159897 | Drug Info | Terminated | Anxiety disorder | [15], [16] | |
L-732138 | Drug Info | Terminated | Discovery agent | [17] | |
MEN-10207 | Drug Info | Terminated | Pain | [18] | |
MEN-10627 | Drug Info | Terminated | Asthma | [19], [20] | |
UK-290795 | Drug Info | Terminated | Urinary incontinence | [21] | |
ZD-7944 | Drug Info | Terminated | Asthma | [22] | |
Inhibitor | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [23] | ||
A-987306 | Drug Info | [24] | |||
Ac-Phe-[Orn-Pro-cha-Trp-Arg] | Drug Info | [25] | |||
Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2 | Drug Info | [25] | |||
L-732138 | Drug Info | [26] | |||
WAY-207024 | Drug Info | [27] | |||
Modulator | AVE-5883 | Drug Info | [28] | ||
DNK-333 | Drug Info | ||||
FK-224 | Drug Info | [29] | |||
GR-159897 | Drug Info | [30] | |||
MEN-10207 | Drug Info | [31] | |||
MEN-10627 | Drug Info | [32] | |||
ZD-6021 | Drug Info | ||||
ZD-7944 | Drug Info | [33] | |||
Antagonist | AZD-5106 | Drug Info | [34] | ||
CS-003 | Drug Info | [8] | |||
GR100679 | Drug Info | [35] | |||
GR94800 | Drug Info | [36] | |||
Ibodutant | Drug Info | [37] | |||
MEN13510 | Drug Info | [38] | |||
Nepadutant | Drug Info | [3] | |||
R396 | Drug Info | [39] | |||
Saredutant | Drug Info | [40], [41], [42] | |||
SCH 206272 | Drug Info | [43] | |||
SLV-332 | Drug Info | [5] | |||
SR 144190 | Drug Info | [44], [45] | |||
UK-224671 | Drug Info | [46] | |||
UK-290795 | Drug Info | [47] | |||
YM44778 | Drug Info | [48] | |||
YM44781 | Drug Info | [48] | |||
YM49598 | Drug Info | [48] | |||
ZM 253270 | Drug Info | [49] | |||
ZM-274773 | Drug Info | [50] | |||
[3H]saredutant | Drug Info | [51] | |||
Agonist | neurokinin A | Drug Info | [52] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Calcium signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
Reactome | G alpha (q) signalling events | ||||
WikiPathways | Gastrin-CREB signalling pathway via PKC and MAPK | ||||
Peptide GPCRs | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
REF 1 | ClinicalTrials.gov (NCT02320318) 12-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D). U.S. National Institutes of Health. | ||||
REF 2 | (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: 2117). | ||||
REF 3 | Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26. | ||||
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: 2123). | ||||
REF 5 | Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. | ||||
REF 6 | Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. | ||||
REF 7 | (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: 2111). | ||||
REF 8 | Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. | ||||
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: 2103). | ||||
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 800001455) | ||||
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 800021516) | ||||
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 800008589) | ||||
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 800010850) | ||||
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 800015341) | ||||
REF 15 | (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: 2115). | ||||
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 800003215) | ||||
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 800006439) | ||||
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 800003687) | ||||
REF 19 | (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: 3901). | ||||
REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004991) | ||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017162) | ||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007349) | ||||
REF 23 | 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 24 | J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia. | ||||
REF 25 | Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. Epub 2006 Jul 28.Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivoactivity. | ||||
REF 26 | J Med Chem. 2010 Aug 12;53(15):5491-501.Biological and conformational evaluation of bifunctional compounds for opioid receptor agonists and neurokinin 1 receptor antagonists possessing two penicillamines. | ||||
REF 27 | 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 28 | Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007 Mar 1;175(5):450-7. Epub 2006 Dec 14. | ||||
REF 29 | FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J Pharmacol Exp Ther. 1992 Jul;262(1):398-402. | ||||
REF 30 | GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors. Eur J Pharmacol. 1995 Jan 16;272(2-3):241-8. | ||||
REF 31 | Role of D-tryptophan for affinity of MEN 10207 tachykinin antagonist at NK2 receptors. Peptides. 1991 Sep-Oct;12(5):1015-8. | ||||
REF 32 | MEN 10,627, a novel polycyclic peptide antagonist of tachykinin NK2 receptors. J Pharmacol Exp Ther. 1994 Dec;271(3):1489-500. | ||||
REF 33 | Discovery of novel, orally active dual NK1/NK2 antagonists. Bioorg Med Chem Lett. 2001 Oct 22;11(20):2769-73. | ||||
REF 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015341) | ||||
REF 35 | Characterisation, CNS distribution and function of NK2 receptors studied using potent NK2 receptor antagonists. Regul Pept. 1993 Jul 2;46(1-2):9-19. | ||||
REF 36 | Synthesis and characterization of selective fluorescent ligands for the neurokinin NK2 receptor. J Med Chem. 1994 Jun 24;37(13):1991-5. | ||||
REF 37 | Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Oct 24. pii: S0014-2999(13)00788-7. | ||||
REF 38 | Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11. | ||||
REF 39 | Characterization of the binding sites of [3H]SR 48968, a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor. Biochem Biophys Res Commun. 1993 Mar 31;191(3):1172-7. | ||||
REF 40 | Occurrence and pharmacological characterization of four human tachykinin NK2 receptor variants. Biochem Pharmacol. 2008 Aug 15;76(4):476-81. Epub 2008 Jun 13. | ||||
REF 41 | Multifaceted approach to determine the antagonist molecular mechanism and interaction of ibodutant ([1-(2-phenyl-1R-[[1-(tetrahydropyran-4-ylmethyl)-piperidin-4-ylmethyl]-carbamoyl]-ethylcarbamoyl)-cyclopentyl]-amide) at the human tachykinin NK2 receptor. J Pharmacol Exp Ther. 2009 May;329(2):486-95. Epub 2009 Feb 13. | ||||
REF 42 | Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3. Biochem Pharmacol. 2009 May 1;77(9):1522-30. Epub 2009 Feb 6. | ||||
REF 43 | SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. Eur J Pharmacol. 2002 Aug 23;450(2):191-202. | ||||
REF 44 | Antagonists at the neurokinin receptors--recent patent literature. IDrugs. 2003 Aug;6(8):758-72. | ||||
REF 45 | Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract. Am J Vet Res. 2004 Jul;65(7):984-91. | ||||
REF 46 | Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42. | ||||
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 800017162) | ||||
REF 48 | Effect of YM-44781, YM-44778 and YM-49598, novel tachykinin antagonists, in a drug-induced bladder contraction model. Pharmacology. 2002 May;65(2):96-102. | ||||
REF 49 | Pharmacological characterization of a new class of nonpeptide neurokinin A antagonists that demonstrate species selectivity. J Pharmacol Exp Ther. 1995 Sep;274(3):1216-21. | ||||
REF 50 | Tachykinin NK2 receptor antagonists. A patent review (2006 - 2010). Expert Opin Ther Pat. 2012 Jan;22(1):57-77. | ||||
REF 51 | Expression of rat NK-2 (neurokinin A) receptor in E. coli. Receptors Channels. 1994;2(4):295-302. | ||||
REF 52 | Structure-activity relationships of neurokinin A (4-10) at the human tachykinin NK(2) receptor: the role of natural residues and their chirality. Biochem Pharmacol. 2001 Jan 1;61(1):55-60. |
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