Details of the Drug Therapeutic Target (DTT)

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]
• Related Disease: Irritable bowel syndrome [ICD-11: DD91]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NK2R_HUMAN
• TTD ID: T52790
• 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.
• Reactome Pathway: G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) 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]

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], [6], [7], [8]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[9]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[10]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[11], [12], [13]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[14]
SR 144190	DMK4XT8	Acute or chronic pain	MG30-MG31	Discontinued in Phase 1	[15], [16]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[17]
AZD-5106	DMABY43	Urinary incontinence	MF50.2	Terminated	[19]
GR-159897	DMLQ71Y	Anxiety disorder	6B00-6B0Z	Terminated	[20]
L-732138	DMVXKMF	N. A.	N. A.	Terminated	[21]
MEN-10207	DM185DR	Pain	MG30-MG3Z	Terminated	[22]
MEN-10627	DM35ABD	Asthma	CA23	Terminated	[23]
UK-290795	DMQFSAB	Urinary incontinence	MF50.2	Terminated	[24]
ZD-7944	DMCT1IX	Asthma	CA23	Terminated	[25]

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	[18]

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	[26]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[27]
GR100679	DMP1DO4	Discovery agent	N.A.	Investigative	[28]
GR94800	DMBYK0X	Discovery agent	N.A.	Investigative	[29]
Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2	DMHW2DU	Discovery agent	N.A.	Investigative	[2]
neurokinin A	DM9UXRP	Discovery agent	N.A.	Investigative	[30]
R396	DM1OPZ9	Discovery agent	N.A.	Investigative	[31]
SCH 206272	DMD1M24	Discovery agent	N.A.	Investigative	[32]
WAY-207024	DMJ14NE	Discovery agent	N.A.	Investigative	[33]
YM44778	DMDOR2L	Discovery agent	N.A.	Investigative	[34]
YM44781	DM73AEL	Discovery agent	N.A.	Investigative	[34]
YM49598	DMTYSUN	Discovery agent	N.A.	Investigative	[34]
ZD-6021	DM8MXS6	Discovery agent	N.A.	Investigative	[35], [35], [36]
ZM 253270	DMA3M9H	Discovery agent	N.A.	Investigative	[37]
ZM-274773	DMD0NFL	Discovery agent	N.A.	Investigative	[38]

Molecular Expression Atlas (MEA) 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

References

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