NEPADUTANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C45H58N10O13
Molecular Weight	947.0012
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@@H]1NC(=O)[C@@H]2CNC(=O)C[C@H](NC(=O)[C@H](CC(=O)N[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3NC(C)=O)NC1=O)C(=O)N[C@@H](CC4=CNC5=C4C=CC=C5)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N2

InChI

InChIKey=NGCNKEZHGRXHNL-WVWQGFTISA-N

InChI=1S/C45H58N10O13/c1-21(2)13-27-39(62)53-31(17-35(59)55-45-36(48-22(3)57)38(61)37(60)33(20-56)68-45)43(66)52-30-16-34(58)47-19-32(44(67)49-27)54-40(63)28(14-23-9-5-4-6-10-23)50-41(64)29(51-42(30)65)15-24-18-46-26-12-8-7-11-25(24)26/h4-12,18,21,27-33,36-38,45-46,56,60-61H,13-17,19-20H2,1-3H3,(H,47,58)(H,48,57)(H,49,67)(H,50,64)(H,51,65)(H,52,66)(H,53,62)(H,54,63)(H,55,59)/t27-,28-,29-,30-,31-,32-,33+,36+,37+,38+,45+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C45H58N10O13
Molecular Weight	947.0012
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	11 / 11
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800010869 | https://www.ncbi.nlm.nih.gov/pubmed/9484857

Menarini was developing oral nepadutant (MEN 11420), a potent and selective tachykinin neurokinin-2 receptor antagonist, for the treatment of infant colic. Nepadutant has been used in trials studying the treatment of colic, infantile colic, and infantile functional gastrointestinal disorders. MEN 11420 is a glycosylated derivative of the potent, selective, conformationally-constrained tachykinin NK2 receptor antagonist MEN 10627. MEN 11420 competitively bound with high affinity to the human NK2 receptor stably transfected in CHO cells, displacing radiolabelled [125I]-neurokinin A and [3H]-SR 48968 with Ki values of 2.5+/-0.7 nM (n = 6) and 2.6+/-0.4 nM (n = 3), respectively.

Originator

Approval Year

PubMed

Title	Date	PubMed
MEN 11420 (Nepadutant), a novel glycosylated bicyclic peptide tachykinin NK2 receptor antagonist.	1998 Jan	9484857
Nepadutant pharmacokinetics and dose-effect relationships as tachykinin NK2 receptor antagonist are altered by intestinal inflammation in rodent models.	2001 Oct	11561086
Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor.	2005 Jun 1	15925360
MEN15596, a novel nonpeptide tachykinin NK2 receptor antagonist.	2006 Nov 7	16979621

Sample Use Guides

In Vivo Use Guide

Infantile Colic: 0.1 - 0.5 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)

Route of Administration: Oral

In Vitro Use Guide

Nepadutant (MEN 11420) competitively bound with high affinity to the human NK2 receptor stably transfected in CHO cells, displacing radiolabelled [125I]-neurokinin A and [3H]-SR 48968 with Ki values of 2.5±0.7 nM (n=6) and 2.6±0.4 nM (n=3), respectively. In the rabbit isolated pulmonary artery and rat urinary bladder MEN 11420 potently and competitively antagonized tachykinin NK2 receptor-mediated contractions (pKB=8.6±0.07, n=10, and 9.0±0.04, n=12; Schild plot slope=−1.06 (95% c.l.=−1.3; −0.8) and −1.17 (95% c.l.=−1.3; −1.0), respectively). MEN 11420 produced an insurmountable antagonism at NK2 receptors in the hamster trachea and mouse urinary bladder. However, in both preparations, the effect of MEN 11420 was reverted by washout and an apparent pKB of 10.2±0.14, n= 9, and 9.8±0.15, n=9, was calculated in the hamster trachea and mouse urinary bladder, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:16:38 UTC 2023` Edited by `admin` on `Fri Dec 15 16:16:38 UTC 2023`
Record UNII	XW59TYL1XH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NEPADUTANT

Official Name

English

CYCLO(N-(2-ACETAMIDO-2-DEOXY-.BETA.-D-GLUCOPYRANOSYL)-L-ASPARAGINYL-L-.ALPHA.-ASPARTYL-L-TRYPTOPHYL-L-PHENYLALANYL-L-2,3-DIAMINOPROPIONYL-L-LEUCYL),CYCLIC(2-5)-PEPTIDE

Common Name

English

nepadutant [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29712