Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTVFO0U)

• DTT Name: Gastrin/cholecystokinin type B receptor (CCKBR) DTT Info
• Gene Name: CCKBR

Molecule-Related Drug & Molecule List

2 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ceruletide	DM2WE5K	Caerulein stimulated gastric and pancreatic secretion	5A4Y	Approved	[1]
Pentagastrin	DMRCLZB	Diagnostic imaging	N.A.	Approved	[2]

9 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GASTRAZOLE	DMO3ITF	Duodenal ulcer	DA63	Phase 3	[3]
Dexloxiglumide	DM52HUD	Pancreatic malfunction	DC30-DC3Z	Phase 2	[4]
Itriglumide	DM5UFRO	Anxiety disorder	6B00-6B0Z	Phase 2	[5]
S-0509	DM4KWEF	Ulcerative colitis	DD71	Phase 2	[6]
Spiroglumide	DM7NJWY	Stomach disease	DA43-DA4Y	Phase 2	[7]
TT-223	DMCDMFP	Type-1 diabetes	5A10	Phase 2	[8]
YF-476	DM54MAJ	Stomach ulcer	DA60.Z	Phase 2	[9]
Z 360	DM2M80G	Discovery agent	N.A.	Phase 2	[10]
Demogastrin	DMTULGS	Thyroid cancer	2D10	Phase 1	[11]

13 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GV-150013	DMZD023	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[12]
L-365260	DMT13ZR	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[13]
PD-134308	DM80UNM	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[14]
CR-2093	DMWVBGD	Intestine cancer	2C0Z	Discontinued in Phase 1	[15]
AG-041R	DM625LN	Ulcerative colitis	DD71	Terminated	[18]
FR-208419	DMLG426	Dyspepsia	MD92	Terminated	[19]
GR-199114X	DMA7FX1	Stomach ulcer	DA60.Z	Terminated	[20]
IQM-95333	DMYCPFU	N. A.	N. A.	Terminated	[4]
LY288513	DMG8YE9	Anxiety disorder	6B00-6B0Z	Terminated	[21]
PD-135666	DMLEVNC	N. A.	N. A.	Terminated	[22]
PD136450	DMD6L82	N. A.	N. A.	Terminated	[23]
SNF-9007	DM4CNM9	N. A.	N. A.	Terminated	[24]
YM-022	DM97ULM	Gastrointestinal disease	DE2Z	Terminated	[25]

3 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GG-8573	DMFQI38	Obesity	5B81	Preclinical	[16]
JNJ-26070109	DMSXOPE	Gastroesophageal reflux disease	DA22.Z	Preclinical	[17]
PD-170292	DMEOVDQ	Obesity	5B81	Preclinical	[16]

58 Investigative Drug(s) Transported by This DTP

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]
Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe	DMKAHYQ	Discovery agent	N.A.	Investigative	[27]
BC-264	DMQWOZ5	Discovery agent	N.A.	Investigative	[28]
Boc-Asp-Tyr(So3-)-Nle-Gly-Trp-Asp-Phe-NH2	DMPJR98	Discovery agent	N.A.	Investigative	[29]
CCK-33	DM1N0ED	Discovery agent	N.A.	Investigative	[30]
CCK-8	DMN0J4W	N. A.	N. A.	Investigative	[30]
Cholecystokinin-9	DMVJMG8	Discovery agent	N.A.	Investigative	[31]
CI-1015	DMQ5CE1	Discovery agent	N.A.	Investigative	[32]
desulfated cholecystokinin-8	DMW740T	Discovery agent	N.A.	Investigative	[33]
GW-5823	DMCOYF9	Discovery agent	N.A.	Investigative	[34]
H-Tyr-D-Ala-Gly-Phe-NH-NH-D-Trp-Nle-Asp-Phe-Bo	DMW50ZQ	Discovery agent	N.A.	Investigative	[35]
H-Tyr-D-Ala-Gly-Phe-NH-NH-D-Trp-Nle-Asp-Phe-H	DMF82C1	Discovery agent	N.A.	Investigative	[35]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-Nle-D-Trp-H	DMSXD63	Discovery agent	N.A.	Investigative	[36]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-Nle-Trp-Ac	DMRUD37	Discovery agent	N.A.	Investigative	[36]
H-Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-Nle-Trp-Boc	DMIPXCZ	Discovery agent	N.A.	Investigative	[36]
PBC-264	DM39LS5	Discovery agent	N.A.	Investigative	[37]
PD-135118	DMUTEWI	Discovery agent	N.A.	Investigative	[22]
PD-135158	DMA7YJV	Discovery agent	N.A.	Investigative	[38]
PD-136621	DM8N3RB	Discovery agent	N.A.	Investigative	[22]
PD-137337	DMJWK0T	Discovery agent	N.A.	Investigative	[22]
PD-137342	DMH2OV9	Discovery agent	N.A.	Investigative	[22]
PD-138915	DMLVRU7	Discovery agent	N.A.	Investigative	[22]
PD-138916	DMIAFN5	Discovery agent	N.A.	Investigative	[22]
PD-138917	DMUG2L9	Discovery agent	N.A.	Investigative	[22]
PD-140547	DMF86P3	Discovery agent	N.A.	Investigative	[22]
PD-140548	DMNO2EP	Discovery agent	N.A.	Investigative	[22]
PD-140723	DMWTOJN	Discovery agent	N.A.	Investigative	[22]
PD-149164	DMP65EI	Discovery agent	N.A.	Investigative	[39]
RB-400	DMJDE6Y	Discovery agent	N.A.	Investigative	[28]
RP-69758	DMXMRVG	Discovery agent	N.A.	Investigative	[40]
RP-71483	DMUFLNT	Discovery agent	N.A.	Investigative	[40]
RP-72540	DMWIXQS	Discovery agent	N.A.	Investigative	[40]
RP73870	DMLKPZ6	Discovery agent	N.A.	Investigative	[41]
RPR-107836	DM9ODEZ	Anxiety disorder	6B00-6B0Z	Investigative	[42]
Tetragastrin	DMDWUCX	Discovery agent	N.A.	Investigative	[43]
tetronothiodin	DM8T7CG	Discovery agent	N.A.	Investigative	[44]
TP-680	DMM41O9	Discovery agent	N.A.	Investigative	[45]
Tyr-D-Ala-Gly-D-Trp-Nle-Asp-Phe-NH2	DM0D1Z5	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Ala-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DMPH1G0	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Ala-Gly-Phe-NH-NH-Phe-Asp-NMeNle-D-Trp-Boc	DMB2TCF	Discovery agent	N.A.	Investigative	[36]
Tyr-D-Ala-Gly-Trp-Nle-Asp-Phe-NH2	DMUXMVQ	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Ala-Gly-Trp-NMeNle-Asp-Phe-NH2	DMREJ69	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Nle-Gly-D-Trp-Nle-Asp-Phe-NH2	DMY9NIJ	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Nle-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DMQREP2	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Nle-Gly-Trp-Nle-Asp-Phe-NH2	DMZ24LN	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Nle-Gly-Trp-NMeNle-Asp-Phe-NH2	DMPSJ72	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Phe-Gly-D-Trp-Nle-Asp-Phe-NH2	DMIWMN6	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Phe-Gly-D-Trp-NMeNle-Asp-Phe-NH2	DM2CEWT	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Phe-Gly-Trp-Nle-Asp-Phe-NH2	DMKM81A	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Phe-Gly-Trp-NMeNle-Asp-Phe-NH2	DMZOTGM	Discovery agent	N.A.	Investigative	[24]
Tyr-D-Pro-Gly-Trp-NMeNle-Asp-Phe-NH2	DMM9H07	Discovery agent	N.A.	Investigative	[24]
Tyr-Gly-Gly-Trp-NMeNle-Asp-Phe-NH2	DMN7290	Discovery agent	N.A.	Investigative	[24]
Tyr-Pro-Gly-Trp-NMeNle-Asp-Phe-NH2	DM8THU2	Discovery agent	N.A.	Investigative	[24]
[125I]-BDZ2	DMYBQOG	Discovery agent	N.A.	Investigative	[46]
[125I]PD142308	DMEHK9M	Discovery agent	N.A.	Investigative	[42]
[3H]JB-93182	DMJCI2A	Discovery agent	N.A.	Investigative	[47]
[3H]PBC-264	DMK46C7	Discovery agent	N.A.	Investigative	[48]
[3H]PD140376	DMWAT5S	Discovery agent	N.A.	Investigative	[49]

References

• [1] Comparison of postprandial and ceruletide serum bile acid stimulation in dogs. J Vet Intern Med. 2008 Jul-Aug;22(4):873-8.
• [2] Functional interactions between endocannabinoid and CCK neurotransmitter systems may be critical for extinction learning. Neuropsychopharmacology. 2009 Jan;34(2):509-21.
• [3] Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials. Br J Cancer. 2006 April 24; 94(8): 1107-1115.
• [4] Synthesis and stereochemical structure-activity relationships of 1,3-dioxoperhydropyrido[1,2-c]pyrimidine derivatives: potent and selective cholecy... J Med Chem. 1997 Oct 10;40(21):3402-7.
• [5] Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases. Curr Top Med Chem. 2007; 7(12): 1211-1231.
• [6] Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs. Aliment Pharmacol Ther. 2000 Apr;14(4):479-88.
• [7] Effect of dexloxiglumide and spiroglumide, two new CCK-receptor antagonists, on gastric emptying and secretion in the rat: evaluation of their receptor selectivity in vivo. Aliment Pharmacol Ther. 1996 Jun;10(3):411-9.
• [8] The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Int J Obes Relat Metab Disord. 2000 Mar;24(3):288-98.
• [9] CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs. Scand J Gastroenterol. 2004 Sep;39(9):886-90.
• [10] Z-360, a novel cholecystokinin-2/gastrin receptor antagonist, inhibits gemcitabine-induced expression of the vascular endothelial growth factor gen... Biol Pharm Bull. 2010;33(2):216-22.
• [11] Demonstration of new sites of expression of the CCK-B/gastrin receptor in pancreatic acinar AR42J cells using immunoelectron microscopy. Regul Pept. 1999 Oct 22;84(1-3):81-9.
• [12] The role of cholecystokinin (CCK), CCK-A or CCK-B receptor antagonists in the spontaneous preference for drugs of abuse (alcohol or cocaine) in naive rats. Methods Find Exp Clin Pharmacol. 1998 Oct;20(8):679-97.
• [13] Pharmacological analysis of CCK(2) receptor ligands using COS-7 and SK-N-MC cells, expressing the human CCK(2) receptor. Regul Pept. 2002 Jan 15;103(1):29-37.
• [14] Comparison of the effects of the cholecystokinin-B receptor antagonist, PD 134308, and the cholecystokinin-A receptor antagonist, L-364,718, on dop... Synapse. 1993 Feb;13(2):117-22.
• [15] Inhibitory effects of the gastrin receptor antagonist CR2093 on basal, gastrin-stimulated and growth factor-stimulated growth of the rat pancreatic cell line AR42J. Anticancer Drugs. 1994 Oct;5(5):591-7.
• [16] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [17] The cholecystokinin CCK2 receptor antagonist, JNJ-26070109, inhibits gastric acid secretion and prevents omeprazole-induced acid rebound in the rat. Br J Pharmacol. 2012 Jul;166(5):1684-93.
• [18] AG-041R, a gastrin/CCK-B antagonist, stimulates chondrocyte proliferation and metabolism in vitro. Biochem Biophys Res Commun. 2001 May 25;283(5):1118-23.
• [19] Dual CCK-A and CCK-B receptor antagonists (II). Preparation and structure activity relationships of 5-alkyl-9-methyl-1,4-benzodiazepines and discovery of FR208419. Chem Pharm Bull (Tokyo). 2000 Jan;48(1):1-15.
• [20] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009210)
• [21] Behavioral and neurochemical study on the role of the brain cholecystokinin system in anxiety. Hokkaido Igaku Zasshi. 1998 Sep;73(5):463-73.
• [22] Selective ligands for cholecystokinin receptor subtypes CCK-A and CCK-B within a single structural class, Bioorg. Med. Chem. Lett. 3(5):881-884 (1993).
• [23] Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat. Gut. 1994 Feb;35(2):270-4.
• [24] Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors. J Med Chem. 2006 May 18;49(10):2868-75.
• [25] YM022, a potent and selective gastrin/CCK-B receptor antagonist, inhibits peptone meal-induced gastric acid secretion in Heidenhain pouch dogs. Dig Dis Sci. 1997 Apr;42(4):707-14.
• [26] 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.
• [27] The rational design and synthesis of non-peptide hegnylogues of CCK-26-33 - a novel series of CCK-A selective ligands, Bioorg. Med. Chem. Lett. 3(5):889-894 (1993).
• [28] Synthesis and biological characterisation of [3H]BBL454, a new CCK2 selective radiolabelled agonist displaying original pharmacological properties. Bioorg Med Chem Lett. 2004 Jan 19;14(2):369-72.
• [29] Synthesis and biological activities of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin. On the importance of the peptide ... J Med Chem. 1987 Aug;30(8):1366-73.
• [30] Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. J Biol Chem. 1993 Aug 25;268(24):18300-5.
• [31] 5-(tryptophylamino)-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based cholecystokinin receptor antagonists: reversal of CCK1 receptor subtype selectiv... J Med Chem. 2004 Oct 7;47(21):5318-29.
• [32] Second generation "peptoid" CCK-B receptor antagonists: identification and development of N-(adamantyloxycarbonyl)-alpha-methyl-(R)-tryptophan derivative (CI-1015) with an improved pharmacokinetic profile. J Med Chem. 1998 Jan 1;41(1):38-45.
• [33] The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J Biol Chem. 1993 Apr 15;268(11):8164-9.
• [34] Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists. J Med Chem. 1997 Aug 15;40(17):2706-25.
• [35] Partial retro-inverso, retro, and inverso modifications of hydrazide linked bifunctional peptides for opioid and cholecystokinin (CCK) receptors. J Med Chem. 2007 Jan 11;50(1):165-8.
• [36] Design and synthesis of novel hydrazide-linked bifunctional peptides as delta/mu opioid receptor agonists and CCK-1/CCK-2 receptor antagonists. J Med Chem. 2006 Mar 9;49(5):1773-80.
• [37] His381 of the rat CCKB receptor is essential for CCKB versus CCKA receptor antagonist selectivity. Eur J Pharmacol. 1996 Jan 18;296(1):97-106.
• [38] Pharmacological characterization of a Chinese hamster ovary cell line transfected with the human CCK-B receptor gene. Neuropeptides. 1996 Aug;30(4):359-63.
• [39] Cholecystokinin B antagonists. Synthesis and quantitative structure-activity relationships of a series of C-terminal analogues of CI-988. Bioorg Med Chem. 1996 Oct;4(10):1733-45.
• [40] Pharmacological properties of ureido-acetamides, new potent and selective non-peptide CCKB/gastrin receptor antagonists. Eur J Pharmacol. 1994 Sep 12;262(3):233-45.
• [41] Pharmacological analysis of CCK2 receptor antagonists using isolated rat stomach ECL cells. Br J Pharmacol. 1999 May;127(2):530-6.
• [42] URL: 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. (Target id: 77).
• [43] Synthesis and binding affinities of analogues of cholecystokinin-(30-33) as probes for central nervous system cholecystokinin receptors. J Med Chem. 1987 Apr;30(4):729-32.
• [44] Species specificity of pharmacological characteristics of CCK-B receptors. Neurosci Lett. 1993 Aug 6;158(1):1-4.
• [45] Pharmacological profile of TP-680, a new cholecystokininA receptor antagonist. Br J Pharmacol. 1996 Apr;117(7):1558-64.
• [46] Synthesis and in vitro characterization of radioiodinatable benzodiazepines selective for type 1 and type 2 cholecystokinin receptors. J Med Chem. 2009 Apr 9;52(7):2138-47.
• [47] Characterization of the binding of a novel radioligand to CCKB/gastrin receptors in membranes from rat cerebral cortex. Br J Pharmacol. 1999 Mar;126(6):1504-12.
• [48] [3H]pBC 264, a suitable probe for studying cholecystokinin-B receptors: binding characteristics in rodent brains and comparison with [3H]SNF 8702. Mol Pharmacol. 1992 Jun;41(6):1089-95.
• [49] [3H]PD 140376: a novel and highly selective antagonist radioligand for the cholecystokininB/gastrin receptor in guinea pig cerebral cortex and gastric mucosa. Mol Pharmacol. 1993 Apr;43(4):595-602.