General Information of Drug Therapeutic Target (DTT) (ID: TTYO0A3)

DTT Name Substance-K receptor (TACR2)
Synonyms Tachykinin receptor 2; Tachykinin neurokinin 2 receptor; TACR2; SKR; Neurokinin A receptor; NK-2R; NK-2 receptor
Gene Name TACR2
DTT Type
Clinical trial target
[1]
BioChemical Class
GPCR rhodopsin
UniProt ID
NK2R_HUMAN
TTD ID
T52790
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGTCDIVTEANISSGPESNTTGITAFSMPSWQLALWATAYLALVLVAVTGNAIVIWIILA
HRRMRTVTNYFIVNLALADLCMAAFNAAFNFVYASHNIWYFGRAFCYFQNLFPITAMFVS
IYSMTAIAADRYMAIVHPFQPRLSAPSTKAVIAGIWLVALALASPQCFYSTVTMDQGATK
CVVAWPEDSGGKTLLLYHLVVIALIYFLPLAVMFVAYSVIGLTLWRRAVPGHQAHGANLR
HLQAMKKFVKTMVLVVLTFAICWLPYHLYFILGSFQEDIYCHKFIQQVYLALFWLAMSST
MYNPIIYCCLNHRFRSGFRLAFRCCPWVTPTKEDKLELTPTTSLSTRVNRCHTKETLFMA
GDTAPSEATSGEAGRPQDGSGLWFGYGLLAPTKTHVEI
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.
KEGG Pathway
Calcium signaling pathway (hsa04020 )
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
G alpha (q) signalling events (R-HSA-416476 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ibodutant DMT67EH Irritable bowel syndrome DD91.0 Phase 3 [1]
PMX-53 DMZUAJ4 Atopic dermatitis EA80 Phase 2 [2]
Rambazole DMP2DNS Psoriasis vulgaris EA90 Phase 2 [3]
Nepadutant DMPMF6L Infantile colics DD93.1 Phase 1/2 [4]
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14 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Saredutant DMSRJY3 Anxiety disorder 6B00-6B0Z Discontinued in Phase 3 [5]
CS-003 DM1AEVT Chronic obstructive pulmonary disease CA22 Discontinued in Phase 2 [6]
DNK-333 DM4ZO01 Irritable bowel syndrome DD91.0 Discontinued in Phase 2 [7]
FK-224 DM1JUS0 Asthma CA23 Discontinued in Phase 2 [8]
AVE-5883 DM3P84V Asthma CA23 Discontinued in Phase 1/2 [9]
SR 144190 DMK4XT8 Acute or chronic pain MG30-MG31 Discontinued in Phase 1 [10]
UK-224671 DMDTRJB Urinary incontinence MF50.2 Discontinued in Phase 1 [11]
AZD-5106 DMABY43 Urinary incontinence MF50.2 Terminated [13]
GR-159897 DMLQ71Y Anxiety disorder 6B00-6B0Z Terminated [14]
L-732138 DMVXKMF N. A. N. A. Terminated [15]
MEN-10207 DM185DR Pain MG30-MG3Z Terminated [16]
MEN-10627 DM35ABD Asthma CA23 Terminated [17]
UK-290795 DMQFSAB Urinary incontinence MF50.2 Terminated [18]
ZD-7944 DMCT1IX Asthma CA23 Terminated [19]
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⏷ Show the Full List of 14 Discontinued Drug(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
SLV-332 DMY9DA3 Irritable bowel syndrome DD91.0 Preclinical [12]
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15 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one DMM9X0G Discovery agent N.A. Investigative [20]
A-987306 DMU34BK Discovery agent N.A. Investigative [21]
GR100679 DMP1DO4 Discovery agent N.A. Investigative [22]
GR94800 DMBYK0X Discovery agent N.A. Investigative [23]
Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2 DMHW2DU Discovery agent N.A. Investigative [2]
neurokinin A DM9UXRP Discovery agent N.A. Investigative [24]
R396 DM1OPZ9 Discovery agent N.A. Investigative [25]
SCH 206272 DMD1M24 Discovery agent N.A. Investigative [26]
WAY-207024 DMJ14NE Discovery agent N.A. Investigative [27]
YM44778 DMDOR2L Discovery agent N.A. Investigative [28]
YM44781 DM73AEL Discovery agent N.A. Investigative [28]
YM49598 DMTYSUN Discovery agent N.A. Investigative [28]
ZD-6021 DM8MXS6 Discovery agent N.A. Investigative [29]
ZM 253270 DMA3M9H Discovery agent N.A. Investigative [30]
ZM-274773 DMD0NFL Discovery agent N.A. Investigative [31]
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⏷ Show the Full List of 15 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Chronic obstructive pulmonary disease CA23 Lung tissue 2.83E-01 0.09 0.35
Chronic obstructive pulmonary disease CA23 Small airway epithelium 1.75E-04 0.12 0.45
Asthma CA23 Nasal and bronchial airway 4.95E-01 -0.08 -0.2
Major depressive disorder 6A20 Pre-frontal cortex 6.83E-01 -2.22E-03 -0.01
Irritable bowel syndrome DD91.0 Rectal colon tissue 1.39E-02 -0.17 -0.46
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References

1 Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Nov 15;720(1-3):180-5.
2 Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
3 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.
4 Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
5 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.
6 Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
7 Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
8 Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerv... J Pharmacol Exp Ther. 1992 Jul;262(1):403-8.
9 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.
10 Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract. Am J Vet Res. 2004 Jul;65(7):984-91.
11 Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
12 Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
13 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015341)
14 GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors. Eur J Pharmacol. 1995 Jan 16;272(2-3):241-8.
15 Biological and conformational evaluation of bifunctional compounds for opioid receptor agonists and neurokinin 1 receptor antagonists possessing tw... J Med Chem. 2010 Aug 12;53(15):5491-501.
16 Role of D-tryptophan for affinity of MEN 10207 tachykinin antagonist at NK2 receptors. Peptides. 1991 Sep-Oct;12(5):1015-8.
17 MEN 10,627, a novel polycyclic peptide antagonist of tachykinin NK2 receptors. J Pharmacol Exp Ther. 1994 Dec;271(3):1489-500.
18 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017162)
19 Discovery of novel, orally active dual NK1/NK2 antagonists. Bioorg Med Chem Lett. 2001 Oct 22;11(20):2769-73.
20 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 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
21 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... J Med Chem. 2008 Nov 27;51(22):7094-8.
22 Characterisation, CNS distribution and function of NK2 receptors studied using potent NK2 receptor antagonists. Regul Pept. 1993 Jul 2;46(1-2):9-19.
23 Synthesis and characterization of selective fluorescent ligands for the neurokinin NK2 receptor. J Med Chem. 1994 Jun 24;37(13):1991-5.
24 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.
25 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.
26 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.
27 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 ... J Med Chem. 2009 Apr 9;52(7):2148-52.
28 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.
29 Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors. J Pharmacol Exp Ther. 2001 Jul;298(1):307-15.
30 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.
31 Tachykinin NK2 receptor antagonists. A patent review (2006 - 2010). Expert Opin Ther Pat. 2012 Jan;22(1):57-77.