MECLINERTANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C32H31ClN4O5
Molecular Weight	587.065
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC(OC)=C1C2=CC(=NN2C3=C4C=CC(Cl)=CC4=NC=C3)C(=O)NC5(C6CC7CC(C6)CC5C7)C(O)=O

InChI

InChIKey=DYLJVOXRWLXDIG-UHFFFAOYSA-N

InChI=1S/C32H31ClN4O5/c1-41-27-4-3-5-28(42-2)29(27)26-16-24(36-37(26)25-8-9-34-23-15-21(33)6-7-22(23)25)30(38)35-32(31(39)40)19-11-17-10-18(13-19)14-20(32)12-17/h3-9,15-20H,10-14H2,1-2H3,(H,35,38)(H,39,40)

HIDE SMILES / InChI

Molecular Formula	C32H31ClN4O5
Molecular Weight	587.065
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8380498
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/7754478 | http://adisinsight.springer.com/drugs/800002937

Meclinertant (SR-48692) is the first non-peptide antagonist of neurotensin receptors. It is potent and selective vs the high-affinity binding sites and with a small activity on the levocabastine-sensitive binding sites. It is active on several species including man without partial agonist properties. In vivo, it is active by oral route with a long duration of action and it is able to cross the blood-brain barrier. Meclinertant may be considered a powerful tool for investigating the role of neurotensin in physiological and pathological processes. Meclinertant has been developing for the treatment of anorexia nervosa; colorectal cancer; irritable bowel syndrome; pain; pancreatic cancer; prostate cancer; schizophrenia; small cell lung cancer however its development was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neurotensin receptor 1 2 Target ID: CHEMBL4123 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8380498	Antagonist 2778		19.3 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Lung cancer 69 Sources: http://adisinsight.springer.com/drugs/800002937	Primary	Phase III 656	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15190231	Primary	Not Provided 504	Unknown Approved Use Unknown
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15169685	Primary	Not Provided 504	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
ATP7A 1	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28790113/	no
ATP7B 1	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28790113/	no
MRP2 475	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28790113/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=124950704	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001EF1	https://www.1pchem.com/search?query=1P001EF1
AK Scientific	X5495	https://aksci.com/item_detail.php?cat=X5495
ApexBio Technology	B7484	https://www.apexbt.com/catalogsearch/result/?q=B7484
Axon MedChem	1164	https://www.axonmedchem.com/product/1164
BOC Sciences	146362-70-1	http://www.bocsci.com/description.asp?cas=146362-70-1
Chem Scene	CS-0025250	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0025250
MedChem Express	HY-105189	https://www.medchemexpress.com/search.html?q=HY-105189&ft=&fa=&fp=
MolPort	MolPort-023-276-909	https://www.molport.com/shop/molecule-link/MolPort-023-276-909
MolPort	MolPort-044-727-605	https://www.molport.com/shop/molecule-link/MolPort-044-727-605
Molnova	M11989	https://www.molnova.com/en/serch-list.html?keywords=M11989
MuseChem	R033805	https://www.musechem.com/product/R033805.html
ShangHai Biochempartner	BCP03645	http://www.biochempartner.com/search_BCP03645
Tocris	3721	https://www.tocris.com/search.php?Type=QuickSearch&Value=3721
eMolecules	36366960	https://orderbb.emolecules.com/search/#?query=36366960
eMolecules	46013907	https://orderbb.emolecules.com/search/#?query=46013907

PubMed

Title	Date	PubMed
		252159918
[3H]SR 48692, the first nonpeptide neurotensin antagonist radioligand: characterization of binding properties and evidence for distinct agonist and antagonist binding domains on the rat neurotensin receptor.	1995 May	7746272
Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist.	1997 Feb	9023294
Stable expression of the mouse levocabastine-sensitive neurotensin receptor in HEK 293 cell line: binding properties, photoaffinity labeling, and internalization mechanism.	1998 Feb 13	9480852
Mutagenesis and modeling of the neurotensin receptor NTR1. Identification of residues that are critical for binding SR 48692, a nonpeptide neurotensin antagonist.	1998 Jun 26	9632698
Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2.	2001 Dec	11723247
Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by activation of dopamine D1-type receptors.	2002 Apr	12064480
Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice.	2004 Jul	15165840
Blockade of neurotensin receptors during amphetamine discontinuation indicates individual variability.	2007 Apr	17276509

Patents

Sample Use Guides

In Vivo Use Guide

Placebo-controlled evaluation of meclinertant (SR-48692) 180 mg/day for the treatment of schizophrenia and schizoaffective disorder. Meclinertant (SR-48692) reverses at low dose (80 micrograms/kg) the turning behavior induced by intrastriatal injection of neurotensin in mice with similar potency whatever the route of administration (i.p. or orally) and with a long duration of action (6 hr).

Route of Administration: Other

In Vitro Use Guide

neurotensin (10⁻¹¹-10⁻⁷ M) significantly stimulated the proliferation of PANC-1 and SR 48692 (10⁻¹¹-10⁻⁷ M) alone had no effect on the growth of PANC-1 cells; however, SR 48692 (10⁻¹⁰-10⁻⁶ M) inhibited the stimulatory effect of neurotensin (10⁻⁹ M).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:30:39 GMT 2023` Edited by `admin` on `Fri Dec 15 15:30:39 GMT 2023`
Record UNII	5JBP4SI96H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MECLINERTANT

Official Name

English

meclinertant [INN]

Common Name

English

REMINERTANT

Common Name

English

2-(((1-(7-CHLORO-4-QUINOLINYL)-5-(2,6-DIMETHOXYPHENYL)-1H-PYRAZOL-3-YL)CARBONYL)AMINO)-TRICYCLO(3.3.1.1(SUP 3,7))DECANE-2-CARBOXYLIC ACID

Systematic Name

English

SR48692

Code

English

SR-48692

Code

English

Code System Code Type Description

DRUG BANK

DB06455