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

CCK-8 Drug Info

cholecystokinin 8; cholecystokinin fragment 26-33 amide (sulphated); CCK-8 (sulphated)

Cross-matching ID

PubChem CID

9833444

ChEBI ID

CHEBI:135946

CAS Number

CAS 25126-32-3

TTD Drug ID

DMN0J4W

VARIDT Drug ID

DR00213

ACDINA Drug ID

D01429

General Information of Drug (ID: DMN0J4W)

Molecule-Related Drug Atlas

Molecule Type:

DTT

DTP

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

Discontinued Drug(s)

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Drug(s) Targeting Gastrin/cholecystokinin type B receptor (CCKBR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pentagastrin	DMRCLZB	Diagnostic imaging	N.A.	Approved	[6]
Ceruletide	DM2WE5K	Caerulein stimulated gastric and pancreatic secretion	5A4Y	Approved	[7]
GASTRAZOLE	DMO3ITF	Duodenal ulcer	DA63	Phase 3	[8]
Dexloxiglumide	DM52HUD	Pancreatic malfunction	DC30-DC3Z	Phase 2	[9]
Spiroglumide	DM7NJWY	Stomach disease	DA43-DA4Y	Phase 2	[10]
TT-223	DMCDMFP	Type-1 diabetes	5A10	Phase 2	[11]
Z 360	DM2M80G	Discovery agent	N.A.	Phase 2	[12]
S-0509	DM4KWEF	Ulcerative colitis	DD71	Phase 2	[13]
YF-476	DM54MAJ	Stomach ulcer	DA60.Z	Phase 2	[14]
Itriglumide	DM5UFRO	Anxiety disorder	6B00-6B0Z	Phase 2	[15]
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Drug(s) Targeting Cholecystokinin receptor type A (CCKAR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexloxiglumide	DM52HUD	Pancreatic malfunction	DC30-DC3Z	Phase 2	[16]
proglumide	DM4MF9V	Influenza virus infection	1E30-1E32	Phase 2	[17]
Lintitript	DMS5X94	Obesity	5B81	Discontinued in Phase 2	[18]
Tarazepide	DMX6ZYE	Gastrointestinal disease	DE2Z	Discontinued in Phase 2	[19]
GI 181771	DMIUFS4	Obesity	5B81	Discontinued in Phase 2	[20]
Pranazepide	DMP43IR	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 2	[21]
CE-326597	DMXO49B	Obesity	5B81	Discontinued in Phase 2	[22]
UCL-2000; butabindide	DML51D0	Obesity	5B81	Discontinued in Phase 1	[23]
SSR-125180	DMSOBW2	Obesity	5B81	Discontinued in Phase 1	[24]
T-0632	DML4M5K	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 1	[25]
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Drug(s) Transported By Multidrug resistance-associated protein 2 (ABCC2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[26]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[28]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[29]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[30]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[31]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[32]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[35]
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Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[36]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[37]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[38]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[37]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[39]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[40]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[41]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[42]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[39]
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Drug(s) Transported By Organic anion transporting polypeptide 1B3 (SLCO1B3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[43]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[37]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[44]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[45]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[37]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[46]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[40]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[42]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[47]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[42]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cholecystokinin receptor type A (CCKAR)	TTCG0AL	CCKAR_HUMAN	Agonist	[1]
Gastrin/cholecystokinin type B receptor (CCKBR)	TTVFO0U	GASR_HUMAN	Agonist	[2]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[3]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[4]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[5]

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References

1	Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6728-32.
2	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.
3	Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol. 2005 Oct;68(4):1031-8.
4	Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
5	Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63.
6	Functional interactions between endocannabinoid and CCK neurotransmitter systems may be critical for extinction learning. Neuropsychopharmacology. 2009 Jan;34(2):509-21.
7	Comparison of postprandial and ceruletide serum bile acid stimulation in dogs. J Vet Intern Med. 2008 Jul-Aug;22(4):873-8.
8	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.
9	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.
10	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.
11	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.
12	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.
13	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.
14	CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs. Scand J Gastroenterol. 2004 Sep;39(9):886-90.
15	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.
16	Full agonists of CCK8 containing a nonhydrolyzable sulfated tyrosine residue. J Med Chem. 1989 Feb;32(2):445-9.
17	Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265-8.
18	A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin. Br J Pharmacol. 2008 Jul;154(5):1009-15.
19	Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. J Physiol Pharmacol. 2007 Dec;58 Suppl 6:65-80.
20	Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506.
21	Dual CCK-A and -B receptor antagonists (I) C9-methyl-1,4-benzodiazepines, Bioorg. Med. Chem. Lett. 7(2):169-174 (1997).
22	Obesity Pharmacotherapy: Current Perspectives and Future Directions. Curr Cardiol Rev. 2013 February; 9(1): 33-54.
23	Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
24	US patent application no. 8,748,419, Antagonists.
25	Effect of T-0632, a cholecystokininA receptor antagonist, on experimental acute pancreatitis. Jpn J Pharmacol. 1997 Feb;73(2):105-12.
26	Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport. Antimicrob Agents Chemother. 2006 Jan;50(1):80-7.
27	Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
28	Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
29	Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2. Oncol Lett. 2016 Sep;12(3):2107-2114.
30	Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
31	Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin. J Transl Med. 2008 Oct 4;6:55.
32	Effect of acetaminophen on expression and activity of rat liver multidrug resistance-associated protein 2 and P-glycoprotein. Biochem Pharmacol. 2004 Aug 15;68(4):791-8.
33	Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
34	Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63.
35	Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
36	Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
37	Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
38	Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
39	The effect of SLCO1B115 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B115. Pharmacogenet Genomics. 2008 May;18(5):424-33.
40	Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
41	Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
42	FDA Drug Development and Drug Interactions
43	LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
44	Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
45	Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53.
46	Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
47	Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.