Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCG0AL)

• DTT Name: Cholecystokinin receptor type A (CCKAR)
• Synonyms: CCKAR; CCK-AR; CCK-A receptor
• Gene Name: CCKAR
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: CCKAR_HUMAN
• TTD ID: T28330
• Sequence:
  MDVVDSLLVNGSNITPPCELGLENETLFCLDQPRPSKEWQPAVQILLYSLIFLLSVLGNT
  LVITVLIRNKRMRTVTNIFLLSLAVSDLMLCLFCMPFNLIPNLLKDFIFGSAVCKTTTYF
  MGTSVSVSTFNLVAISLERYGAICKPLQSRVWQTKSHALKVIAATWCLSFTIMTPYPIYS
  NLVPFTKNNNQTANMCRFLLPNDVMQQSWHTFLLLILFLIPGIVMMVAYGLISLELYQGI
  KFEASQKKSAKERKPSTTSSGKYEDSDGCYLQKTRPPRKLELRQLSTGSSSRANRIRSNS
  SAANLMAKKRVIRMLIVIVVLFFLCWMPIFSANAWRAYDTASAERRLSGTPISFILLLSY
  TSSCVNPIIYCFMNKRFRLGFMATFPCCPNPGPPGARGEVGEEEEGGTTGASLSRFSYSH
  MSASVPPQ
• Function: Receptor forcholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Insulin secretion (hsa04911)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexloxiglumide	DM52HUD	Pancreatic malfunction	DC30-DC3Z	Phase 2	[2]
proglumide	DM4MF9V	Influenza virus infection	1E30-1E32	Phase 2	[1]

19 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CE-326597	DMXO49B	Obesity	5B81	Discontinued in Phase 2	[3]
GI 181771	DMIUFS4	Obesity	5B81	Discontinued in Phase 2	[4]
Lintitript	DMS5X94	Obesity	5B81	Discontinued in Phase 2	[5]
Pranazepide	DMP43IR	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 2	[6]
Tarazepide	DMX6ZYE	Gastrointestinal disease	DE2Z	Discontinued in Phase 2	[7]
SR-146131	DML7KCO	Obesity	5B81	Discontinued in Phase 1	[8]
SSR-125180	DMSOBW2	Obesity	5B81	Discontinued in Phase 1	[9]
T-0632	DML4M5K	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 1	[10]
UCL-2000; butabindide	DML51D0	Obesity	5B81	Discontinued in Phase 1	[11]
A-70276	DM9KNFZ	Gastrointestinal disease	DE2Z	Terminated	[12]
A-71623	DMKZNTY	Obesity	5B81	Terminated	[13]
CR-1795	DM8NVZQ	N. A.	N. A.	Terminated	[14]
FR-208419	DMLG426	Dyspepsia	MD92	Terminated	[15]
GI-248573	DMT6J1E	Bladder disease	DC11-DC1Z	Terminated	[9]
IQM-95333	DMYCPFU	N. A.	N. A.	Terminated	[16]
Lorglumide	DM904B6	Pancreatic malfunction	DC30-DC3Z	Terminated	[17]
PD-135666	DMLEVNC	N. A.	N. A.	Terminated	[18]
SNF-9007	DM4CNM9	N. A.	N. A.	Terminated	[19]
SR-27950	DMZ8SXP	Eating disorder	6B82	Terminated	[20]

6 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-71378	DMZ4HMP	Obesity	5B81	Preclinical	[11]
A-74498	DMAK6H3	Obesity	5B81	Preclinical	[11]
AR-R-1589	DMMD8VY	Eating disorder	6B82	Preclinical	[11]
FPL-14294	DMUHVEA	Obesity	5B81	Preclinical	[11]
GG-8573	DMFQI38	Obesity	5B81	Preclinical	[11]
PD-170292	DMEOVDQ	Obesity	5B81	Preclinical	[11]

63 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(3,3-Diphenyl-allyl)-3-m-tolyl-urea	DM6RO2L	Discovery agent	N.A.	Investigative	[21]
1-(4-Chloro-phenyl)-3-(3,3-diphenyl-allyl)-urea	DM3YI5G	Discovery agent	N.A.	Investigative	[21]
1-(4-Chloro-phenyl)-3-(3-pentyl-oct-2-enyl)-urea	DMUW1GI	Discovery agent	N.A.	Investigative	[21]
2-NAP	DM2FTIC	Gastrointestinal disease	DE2Z	Investigative	[22]
3,4-Dichloro-N-(3,3-diphenyl-allyl)-benzamide	DMWOMVF	Discovery agent	N.A.	Investigative	[21]
Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe	DMKAHYQ	Discovery agent	N.A.	Investigative	[23]
Asperlicin	DMAY2N3	Gastrointestinal disease	DE2Z	Investigative	[24]
Bis(31/31')[[Cys(31), Nva(34)]NPY(27-36)-NH(2)]	DMKANOH	Discovery agent	N.A.	Investigative	[25]
Boc-Asp-Tyr(So3-)-Nle-Gly-Trp-Asp-Phe-NH2	DMPJR98	Discovery agent	N.A.	Investigative	[26]
Boc-cyclo-(Glu-Tyr-Nle-D-Lys)-Trp-Nle-Asp-Phe-NH2	DMRQVME	Discovery agent	N.A.	Investigative	[27]
Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2	DMBCPKF	Discovery agent	N.A.	Investigative	[27]
Boc-D-Glu-Tyr(SO3H)-Nle-D-Nle-Trp-Nle-Asp-Phe-NH2	DM1IXOG	Discovery agent	N.A.	Investigative	[27]
Boc-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2	DMN3EU9	Discovery agent	N.A.	Investigative	[27]
Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2	DMAYWTI	Discovery agent	N.A.	Investigative	[27]
CCK-33	DM1N0ED	Discovery agent	N.A.	Investigative	[28]
CCK-8	DMN0J4W	N. A.	N. A.	Investigative	[29]
CI-1015	DMQ5CE1	Discovery agent	N.A.	Investigative	[30]
CR-2345	DMFG0XS	Discovery agent	N.A.	Investigative	[14]
Devazepide	DMD4N2F	Gastrointestinal disease	DE2Z	Investigative	[24]
FR-175985	DMQDP23	Discovery agent	N.A.	Investigative	[6]
Glaxo-11p	DM4QJPU	Discovery agent	N.A.	Investigative	[31]
GW-5823	DMCOYF9	Discovery agent	N.A.	Investigative	[32]
H-Tyr-D-Ala-Gly-Phe-NH-NH-D-Trp-Nle-Asp-Phe-H	DMF82C1	Discovery agent	N.A.	Investigative	[33]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-Nle-D-Trp-H	DMSXD63	Discovery agent	N.A.	Investigative	[34]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-Nle-Trp-Boc	DMIPXCZ	Discovery agent	N.A.	Investigative	[34]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Trp-D-Nle-D-Asp-D-Phe-H	DMFSKDM	Discovery agent	N.A.	Investigative	[33]
IQM-97423	DM2MXIK	Discovery agent	N.A.	Investigative	[35]
JMV180	DM5G0IM	Discovery agent	N.A.	Investigative	[36]
JNJ-17156516	DMIXUNB	Discovery agent	N.A.	Investigative	[37]
KSG-504	DMC92ER	Pancreatic malfunction	DC30-DC3Z	Investigative	[38]
L-708474	DM3QUCS	Discovery agent	N.A.	Investigative	[39]
L-736380	DMM5AYL	Discovery agent	N.A.	Investigative	[40]
L-740093	DMVA2D0	Discovery agent	N.A.	Investigative	[41]
PD-135118	DMUTEWI	Discovery agent	N.A.	Investigative	[18]
PD-135158	DMA7YJV	Discovery agent	N.A.	Investigative	[29]
PD-136621	DM8N3RB	Discovery agent	N.A.	Investigative	[18]
PD-137337	DMJWK0T	Discovery agent	N.A.	Investigative	[18]
PD-137342	DMH2OV9	Discovery agent	N.A.	Investigative	[18]
PD-138915	DMLVRU7	Discovery agent	N.A.	Investigative	[18]
PD-138916	DMIAFN5	Discovery agent	N.A.	Investigative	[18]
PD-140547	DMF86P3	Discovery agent	N.A.	Investigative	[18]
PD-140548	DMNO2EP	Discovery agent	N.A.	Investigative	[18]
PD-140723	DMWTOJN	Discovery agent	N.A.	Investigative	[18]
SC-50998	DMBQ16F	Discovery agent	N.A.	Investigative	[20]
Tetragastrin	DMDWUCX	Discovery agent	N.A.	Investigative	[42]
TP-680	DMM41O9	Discovery agent	N.A.	Investigative	[43]
Tyr-D-Ala-Gly-D-Trp-Nle-Asp-Phe-NH2	DM0D1Z5	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Ala-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DMPH1G0	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-NMeNle-D-Trp-Boc	DMB2TCF	Discovery agent	N.A.	Investigative	[34]
Tyr-D-Ala-Gly-Trp-Nle-Asp-Phe-NH2	DMUXMVQ	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Ala-Gly-Trp-NMeNle-Asp-Phe-NH2	DMREJ69	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Nle-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DMQREP2	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Nle-Gly-Trp-Nle-Asp-Phe-NH2	DMZ24LN	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Phe-Gly-D-Trp-Nle-Asp-Phe-NH2	DMIWMN6	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Phe-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DM2CEWT	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Phe-Gly-Trp-Nle-Asp-Phe-NH2	DMKM81A	Discovery agent	N.A.	Investigative	[19]
Tyr-D-Phe-Gly-Trp-NMeNle-Asp-Phe-NH2	DMZOTGM	Discovery agent	N.A.	Investigative	[19]
VL-0395	DMKW5YL	Discovery agent	N.A.	Investigative	[44]
VL-0494	DM2XAUY	Discovery agent	N.A.	Investigative	[45]
VL-0699	DMCZNB3	Discovery agent	N.A.	Investigative	[46]
VL-1499	DMU9VQJ	Discovery agent	N.A.	Investigative	[44]
VL-2799	DMBEV4W	Discovery agent	N.A.	Investigative	[47]
[3H]devazepide	DM4NXRO	Discovery agent	N.A.	Investigative	[48]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Irritable bowel syndrome	DD91.0	Rectal colon tissue	9.99E-01	-0.03	-0.2

References

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• [3] Obesity Pharmacotherapy: Current Perspectives and Future Directions. Curr Cardiol Rev. 2013 February; 9(1): 33-54.
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• [46] Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes". J Med Chem. 2006 Apr 20;49(8):2456-62.
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• [48] Characterization of the binding of [3H]-(+/-)-L-364,718: a new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors. Mol Pharmacol. 1986 Sep;30(3):212-7.