DEVAZEPIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H20N4O2
Molecular Weight	408.4519
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C2=CC=CC=C2C(=N[C@H](NC(=O)C3=CC4=C(N3)C=CC=C4)C1=O)C5=CC=CC=C5

InChI

InChIKey=NFHRQQKPEBFUJK-HSZRJFAPSA-N

InChI=1S/C25H20N4O2/c1-29-21-14-8-6-12-18(21)22(16-9-3-2-4-10-16)27-23(25(29)31)28-24(30)20-15-17-11-5-7-13-19(17)26-20/h2-15,23,26H,1H3,(H,28,30)/t23-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C25H20N4O2
Molecular Weight	408.4519
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3014519 | https://www.ncbi.nlm.nih.gov/pubmed/3014520
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1713709 | http://adisinsight.springer.com/drugs/800000913

Devazepide (L-364718 or MK-329) is a nonpeptide antagonist for the peripheral (type-A) cholecystokinin (CCK) receptor, which has proved effective in blocking the actions of both exogenous and endogenous CCK in several species. It is an orally active antagonist of CCK-stimulated pancreaticobiliary output in man. Devazepide has been developing for the treatment of anxiety, cancer, neuropathic pain however development discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cholecystokinin A receptor 7 Target ID: CHEMBL1901 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3134624 \| https://www.ncbi.nlm.nih.gov/pubmed/2257485 \| https://www.ncbi.nlm.nih.gov/pubmed/3014520	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7705440	Primary	Preclinical	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1553366	Primary	Phase II 1132	Unknown Approved Use Unknown
Pain 614 Sources: https://www.google.ch/patents/WO2003086409A1?cl=en	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 402 P-gp 1461 CYP19A1 60

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144205297	inconclusive [IC50 8.1995 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466556	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144205297	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466556	yes [IC50 2.754 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144205297	yes [IC50 29.8423 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	yes [IC50 <10 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34120	https://www.001chemical.com/chem/search?q=DY34120
Alfa Chemistry	103420-77-5	http://www.alfa-chemistry.com/search.aspx?q=103420-77-5
MolPort	MolPort-003-666-871	https://www.molport.com/shop/molecule-link/MolPort-003-666-871
Molcore	MC34120	http://www.molcore.com/CatMC34120.html
MuseChem	M011517	https://www.musechem.com/product/M011517.html
Tetrahedron	TS69538	http://www.thsci.com/search.do?q=TS69538
Tocris	2304	https://www.tocris.com/search.php?Type=QuickSearch&Value=2304
Toronto Research Chemicals	D535518	https://www.trc-canada.com/product-detail/?CatNum=D535518
Wonderchem	WD04LPM	http://www.wonder-chem.com/search.html?text=WD04LPM

PubMed

Title	Date	PubMed
Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.	1994 Oct	7524350
Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat.	1997 Oct 3	9372230
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.	1998 Oct	9922984
Melatonin and its precursor, L-tryptophan: influence on pancreatic amylase secretion in vivo and in vitro.	2004 Apr	15009505
Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands.	2008 Jan	18003792
New anthranilic acid based antagonists with high affinity and selectivity for the human cholecystokinin receptor 1 (hCCK1-R).	2011 Aug 25	21728335
Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY.	2012 Dec	22903826

Patents

Sample Use Guides

In Vivo Use Guide

To evaluate the effect of devazepide on CCK-stimulated pancreaticobiliary output in man, six normal subjects received 10 mg MK-329 or placebo orally in a randomized, crossover fashion, before a background intravenous infusion of secretin (5 pmol/kg/h) and two doses of CCK-8 (approximately 15 and 40 pmol/kg/h, each for 1 h).

Route of Administration: Oral

In Vitro Use Guide

Devazepide inhibits the proliferation and induces morphologic changes in the mucous-secreting, autonomously proliferating human cancer colon cell line (HT29-S-B6. Addition of devazepide (10 microM) for at least 3 days in the exponential phase of growth enhanced the baseline production of gastric M1 mucins 2-3-fold and that of carcinoembryonic antigens 5-fold. The production of InsP3 stimulated by 10 nM-CCK-8 was dose-dependently suppressed by the CCK-A antagonist Devazepide in the concentration range 1-10 nM; the effect declined when the concentration was further increased to 100-1000 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:12:13 GMT 2023` Edited by `admin` on `Fri Dec 15 17:12:13 GMT 2023`
Record UNII	JE6P7QY7NH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEVAZEPIDE

Official Name

English

devazepide [INN]

Common Name

English

L-364718

Code

English

(S)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)indole-2-carboxamide

Systematic Name

English

L-364,718

Code

English

1H-INDOLE-2-CARBOXAMIDE, N-(2,3-DIHYDRO-1-METHYL-2-OXO-5-PHENYL-1H-1,4-BENZODIAZEPIN-3-YL)-, (S)-

Common Name

English

DEVAZEPIDE [USAN]

Common Name

English

MK-329

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C547