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

General Information of Drug (ID: DM8N3RB)

• Drug Name: PD-136621 Drug Info
• Synonyms: CHEMBL263969; PD-136621; 4-[(S)-2-[(R)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methylpropanoylamino]-1-phenylethylamino]-4-oxobutyric acid

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 44320702
  TTD Drug ID: DM8N3RB

Molecule-Related Drug Atlas

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	[2]
Ceruletide	DM2WE5K	Caerulein stimulated gastric and pancreatic secretion	5A4Y	Approved	[3]
GASTRAZOLE	DMO3ITF	Duodenal ulcer	DA63	Phase 3	[4]
Dexloxiglumide	DM52HUD	Pancreatic malfunction	DC30-DC3Z	Phase 2	[5]
Spiroglumide	DM7NJWY	Stomach disease	DA43-DA4Y	Phase 2	[6]
TT-223	DMCDMFP	Type-1 diabetes	5A10	Phase 2	[7]
Z 360	DM2M80G	Discovery agent	N.A.	Phase 2	[8]
S-0509	DM4KWEF	Ulcerative colitis	DD71	Phase 2	[9]
YF-476	DM54MAJ	Stomach ulcer	DA60.Z	Phase 2	[10]
Itriglumide	DM5UFRO	Anxiety disorder	6B00-6B0Z	Phase 2	[11]

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	[12]
proglumide	DM4MF9V	Influenza virus infection	1E30-1E32	Phase 2	[13]
Lintitript	DMS5X94	Obesity	5B81	Discontinued in Phase 2	[14]
Tarazepide	DMX6ZYE	Gastrointestinal disease	DE2Z	Discontinued in Phase 2	[15]
GI 181771	DMIUFS4	Obesity	5B81	Discontinued in Phase 2	[16]
Pranazepide	DMP43IR	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 2	[17]
CE-326597	DMXO49B	Obesity	5B81	Discontinued in Phase 2	[18]
UCL-2000; butabindide	DML51D0	Obesity	5B81	Discontinued in Phase 1	[19]
SSR-125180	DMSOBW2	Obesity	5B81	Discontinued in Phase 1	[20]
T-0632	DML4M5K	Pancreatic malfunction	DC30-DC3Z	Discontinued in Phase 1	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

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

References

• [1] 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).
• [2] Functional interactions between endocannabinoid and CCK neurotransmitter systems may be critical for extinction learning. Neuropsychopharmacology. 2009 Jan;34(2):509-21.
• [3] Comparison of postprandial and ceruletide serum bile acid stimulation in dogs. J Vet Intern Med. 2008 Jul-Aug;22(4):873-8.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs. Scand J Gastroenterol. 2004 Sep;39(9):886-90.
• [11] 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.
• [12] Full agonists of CCK8 containing a nonhydrolyzable sulfated tyrosine residue. J Med Chem. 1989 Feb;32(2):445-9.
• [13] Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265-8.
• [14] A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin. Br J Pharmacol. 2008 Jul;154(5):1009-15.
• [15] Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. J Physiol Pharmacol. 2007 Dec;58 Suppl 6:65-80.
• [16] Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506.
• [17] Dual CCK-A and -B receptor antagonists (I) C9-methyl-1,4-benzodiazepines, Bioorg. Med. Chem. Lett. 7(2):169-174 (1997).
• [18] Obesity Pharmacotherapy: Current Perspectives and Future Directions. Curr Cardiol Rev. 2013 February; 9(1): 33-54.
• [19] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [20] US patent application no. 8,748,419, Antagonists.
• [21] Effect of T-0632, a cholecystokininA receptor antagonist, on experimental acute pancreatitis. Jpn J Pharmacol. 1997 Feb;73(2):105-12.