Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZPO1L)

• DTT Name: Substance-P receptor (TACR1)
• Synonyms: Tachykinin receptor 1; Tachykinin neurokinin 1 receptor; Tachykinin 1 receptor; TACR1; Substance P receptor; SPR; Neurokinin 1 receptor; NK-1R; NK-1 receptor
• Gene Name: TACR1
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NK1R_HUMAN
• TTD ID: T47094
• Sequence:
  MDNVLPVDSDLSPNISTNTSEPNQFVQPAWQIVLWAAAYTVIVVTSVVGNVVVMWIILAH
  KRMRTVTNYFLVNLAFAEASMAAFNTVVNFTYAVHNEWYYGLFYCKFHNFFPIAAVFASI
  YSMTAVAFDRYMAIIHPLQPRLSATATKVVICVIWVLALLLAFPQGYYSTTETMPSRVVC
  MIEWPEHPNKIYEKVYHICVTVLIYFLPLLVIGYAYTVVGITLWASEIPGDSSDRYHEQV
  SAKRKVVKMMIVVVCTFAICWLPFHIFFLLPYINPDLYLKKFIQQVYLAIMWLAMSSTMY
  NPIIYCCLNDRFRLGFKHAFRCCPFISAGDYEGLEMKSTRYLQTQGSVYKVSRLETTIST
  VVGAHEEEPEDGPKATPSSLDLTSNCSSRSDSKTMTESFSFSSNVLS
• Function: This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Measles (hsa05162)
• Reactome Pathway: G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[1]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[2]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[3]

19 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[4]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[5]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[2]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[6]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[7]
DAPITANT	DMR5J6K	Pain	MG30-MG3Z	Phase 2	[8]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[3]
GW 597599	DMY53PL	Major depressive disorder	6A70.3	Phase 2	[9]
LANEPITANT	DM1VK96	Pain	MG30-MG3Z	Phase 2	[10]
LY-2590443	DM81UJW	Migraine	8A80	Phase 2	[11]
NKP 608	DMTVGMZ	Mood disorder	6A60-6E23	Phase 2	[12]
Orvepitant	DMSO846	Anxiety disorder	6B00-6B0Z	Phase 2	[3]
SCH-900978	DMPBKUZ	Cough	MD12	Phase 2	[13]
SSR240600	DMVZ01T	Urinary incontinence	MF50.2	Phase 2	[14]
TKA-731	DMT8SMO	Pain	MG30-MG3Z	Phase 2	[15]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[16]
CJ-12255	DMRQX9H	Eczema	EA80-EA89	Phase 1	[17]
Figopitant	DMLH2Q6	Diabetic complication	5A2Y	Phase 1	[18]
GSK1144814	DMK3S9J	Alcohol dependence	6C40.2	Phase 1	[19]

28 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Casopitant	DMBQYO0	Chemotherapy-induced nausea	MD90	Withdrawn from market	[20]
BL-1832	DMLXHZR	Pain	MG30-MG3Z	Discontinued in Phase 3	[21]
L-759274	DMXWRGF	Depression	6A70-6A7Z	Discontinued in Phase 3	[20]
CGP-49823	DMBJQU6	Pain	MG30-MG3Z	Discontinued in Phase 2	[22]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[23]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[24]
Ezlopitant	DMTUPZ2	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[25]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[26]
FK-888	DM457B1	Migraine	8A80	Discontinued in Phase 2	[27]
GSK 679769	DMSV6KP	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[25]
Nolpitantium besilate	DMK5WLZ	Asthma	CA23	Discontinued in Phase 2	[28]
TA-5538	DMBZG2Y	Overactive bladder	GC50.0	Discontinued in Phase 2	[29]
TAK-637	DMDVJKW	Depression	6A70-6A7Z	Discontinued in Phase 2	[20]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[30]
SDZ-NKT-343	DM8C3G5	Pain	MG30-MG3Z	Discontinued in Phase 1	[31]
SLV-323	DMHRYX6	Chemotherapy-induced nausea	MD90	Discontinued in Phase 1	[25]
CI-1021	DMUK9L4	N. A.	N. A.	Terminated	[32]
CP-96345	DM4HYWR	N. A.	N. A.	Terminated	[33]
FK-355	DMIGXQF	Asthma	CA23	Terminated	[34]
FR-113680	DMCAZPR	Asthma	CA23	Terminated	[35]
GR-82334	DMR2TZK	Vomiting	MD90	Terminated	[36]
L-732138	DMVXKMF	N. A.	N. A.	Terminated	[37]
L-733060	DMA1NJW	N. A.	N. A.	Terminated	[38]
L-741671	DMRVXEQ	Vomiting	MD90	Terminated	[39]
MEN-11149	DMEYNB0	Asthma	CA23	Terminated	[40]
MEN-11467	DMNTIWC	Respiratory tract inflammation	CA07	Terminated	[41]
RP-67580	DMDLW64	Pain	MG30-MG3Z	Terminated	[42]
WIN-64821	DM960I8	Asthma	CA23	Terminated	[43]

64 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(D)-Phe-(D)-Phe-NH2	DM5ZIUW	Discovery agent	N.A.	Investigative	[44]
(D)-Phe-(L)-Phe-NH2	DMS32YA	Discovery agent	N.A.	Investigative	[44]
(L)-Phe-(D)-Phe-NH2	DMP9ZVQ	Discovery agent	N.A.	Investigative	[44]
2-Phenyl-3-(1-phenyl-ethoxy)-piperidine	DMNXI6D	Discovery agent	N.A.	Investigative	[38]
3,6-Diphenyl-1-oxa-7-aza-spiro[4.5]decane	DMEOBNJ	Discovery agent	N.A.	Investigative	[45]
3-Benzyloxy-2-phenyl-piperidine	DM94K83	Discovery agent	N.A.	Investigative	[38]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[46]
7-METHYL-8-OXO-5-P-TOLYL-7,8-DIHYDRO-[1,7]NAPHTHYRIDINE-6-CARBOXYLIC ACID (3,5-BIS-TRIFLUOROMETHYL-BENZYL)-METHYL-AMIDE (STRUCTURAL MIX)	DMMENDC	Discovery agent	N.A.	Investigative	[47]
7-METHYL-8-OXO-5-P-TOLYL-7,8-DIHYDRO-[1,7]NAPHTHYRIDINE-6-CARBOXYLIC ACID (S)-[(R)-1-(3,5-BIS-TRIFLUOROMETHYL-PHENYL)-ETHYL]-METHYL-AMIDE (ENANTIOMERIC MIX)	DMO0RGL	Discovery agent	N.A.	Investigative	[47]
7-METHYL-8-OXO-5-P-TOLYL-7,8-DIHYDRO-[1,7]NAPHTHYRIDINE-6-CARBOXYLIC ACID (S)-[(S)-1-(3,5-BIS-TRIFLUOROMETHYL-PHENYL)-ETHYL]-METHYL-AMIDE (ENANTIOMERIC MIX)	DMOAJ0E	Discovery agent	N.A.	Investigative	[47]
Ac-Phe-Phe-NH2	DMDXBQA	Discovery agent	N.A.	Investigative	[44]
Arg-Pro-Lys-Pro-Ala-Gln-Phe-Phe-Gly-Leu-Met-NH2	DM6PA1S	Discovery agent	N.A.	Investigative	[48]
Arg-Pro-Lys-Pro-Ala-Ser-Phe-Phe-Gly-Leu-Met-NH2	DMYM91S	Discovery agent	N.A.	Investigative	[48]
Arg-Pro-Lys-Pro-Gln-Ser-Phe-Phe-Gly-Leu-Met-NH2	DMA318X	Discovery agent	N.A.	Investigative	[48]
befetupitant	DMZX57Y	Discovery agent	N.A.	Investigative	[49]
CP-100263	DMLFNTH	Vomiting	MD90	Investigative	[25]
CP-99,994	DMVJX21	Discovery agent	N.A.	Investigative	[32]
eledoisin	DMEOJ9W	Discovery agent	N.A.	Investigative	[50]
ENDOMORPHIN 2	DMOQWBU	Discovery agent	N.A.	Investigative	[44]
EU-C-001	DMR3487	Brain injury	NA07.Z	Investigative	[11]
H-Ala-Pro-Phe-Phe-NH2	DM5S4AO	Discovery agent	N.A.	Investigative	[44]
H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH	DMJ6N1X	Discovery agent	N.A.	Investigative	[44]
H-Leu-Phe-NH2	DMAPWC2	Discovery agent	N.A.	Investigative	[44]
H-Phe-NH2	DM9IODG	Discovery agent	N.A.	Investigative	[44]
H-Phe-Phe-NH2	DM0KFW2	Discovery agent	N.A.	Investigative	[44]
H-Pro-Phe-Phe-NH2	DMXKPQR	Discovery agent	N.A.	Investigative	[44]
H-Tyr(OMe)-Phe(2-Me)-NH2	DMX08FL	Discovery agent	N.A.	Investigative	[44]
H-Tyr-Ala-Phe-Phe-NH2	DMUHBGC	Discovery agent	N.A.	Investigative	[44]
H-Tyr-D-Ala-Gly Phe-Pro-Leu-Trp-O-3,5-Bzl(CF3)2	DMDF9AS	Discovery agent	N.A.	Investigative	[51]
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-NH-3,5-Bzl(CF3)2	DM2K16M	Discovery agent	N.A.	Investigative	[51]
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-NH-Bzl	DMRE4ZI	Discovery agent	N.A.	Investigative	[51]
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-NMe-3,5-Bzl(CF3)2	DM1ESMZ	Discovery agent	N.A.	Investigative	[51]
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-NMe-Bzl	DM56KDV	Discovery agent	N.A.	Investigative	[51]
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-O-Bzl	DMH3YKR	Discovery agent	N.A.	Investigative	[51]
H-Tyr-Pro-Ala-Phe-NH2	DMP0CRD	Discovery agent	N.A.	Investigative	[44]
H-Tyr-Pro-Phe-Ala-NH2	DM2F6L9	Discovery agent	N.A.	Investigative	[44]
H-Tyr-Pro-Phe-Phe-OH	DMUQLRN	Discovery agent	N.A.	Investigative	[44]
Homspera	DMI7258	Influenza virus infection	1E30-1E32	Investigative	[11]
kassinin	DMMIA38	Discovery agent	N.A.	Investigative	[50]
L-703,606	DMUOPRT	Discovery agent	N.A.	Investigative	[50]
L-708568	DMLMV9P	Discovery agent	N.A.	Investigative	[52]
L-736281	DMJNLSI	Discovery agent	N.A.	Investigative	[39]
MDL-28163	DMUHJ2C	Discovery agent	N.A.	Investigative	[53]
neurokinin A	DM9UXRP	Discovery agent	N.A.	Investigative	[54]
physalaemin	DM09T76	Discovery agent	N.A.	Investigative	[50]
Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2	DMOTXE3	Discovery agent	N.A.	Investigative	[48]
R-226161	DM4BP7S	Discovery agent	N.A.	Investigative	[55]
R116031	DM6Y7QM	Discovery agent	N.A.	Investigative	[56]
S-41744	DMFC430	Major depressive disorder	6A70.3	Investigative	[11]
SCH 206272	DMD1M24	Discovery agent	N.A.	Investigative	[57]
Septide	DMRJIP4	Discovery agent	N.A.	Investigative	[58]
SP-SAP	DMKCJQW	Cancer related pain	MG30	Investigative	[11]
SPANTIDE	DMV63IP	Discovery agent	N.A.	Investigative	[59]
spantide II	DMKC6IX	Discovery agent	N.A.	Investigative	[60]
Substance P	DMQ6W4I	Discovery agent	N.A.	Investigative	[61]
T2328	DMCWE90	Discovery agent	N.A.	Investigative	[62]
Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-Bzl	DMWOP9N	Discovery agent	N.A.	Investigative	[63]
WIN-64745	DMQ1B2Y	Discovery agent	N.A.	Investigative	[64]
WIN-66306	DMUM5LV	Discovery agent	N.A.	Investigative	[65]
WIN-68577	DMJHG1O	Discovery agent	N.A.	Investigative	[65]
ZD-6021	DM8MXS6	Discovery agent	N.A.	Investigative	[66]
[125I]L703,606	DMKSI80	Discovery agent	N.A.	Investigative	[67]
[18F]SPA-RQ	DMXIO84	Discovery agent	N.A.	Investigative	[11]
[Sar9,Met(O2)11]-SP	DMYF85Q	Discovery agent	N.A.	Investigative	[68]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	7.40E-01	0.02	0.07
Schizophrenia	6A20	Superior temporal cortex	8.57E-01	-0.02	-0.18
Chronic obstructive pulmonary disease	CA23	Lung tissue	9.59E-02	-0.05	-0.28
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.38E-01	0.05	0.3
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.94E-01	0.04	0.2
Asthma	CA23	Nasal and bronchial airway	9.91E-01	0.02	0.09
Major depressive disorder	6A20	Pre-frontal cortex	7.24E-01	0.02	0.11

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