LAQUINIMOD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17ClN2O3
Molecular Weight	356.803
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(C(=O)C1=C(O)C2=C(C=CC=C2Cl)N(C)C1=O)C3=CC=CC=C3

InChI

InChIKey=GKWPCEFFIHSJOE-UHFFFAOYSA-N

InChI=1S/C19H17ClN2O3/c1-3-22(12-8-5-4-6-9-12)19(25)16-17(23)15-13(20)10-7-11-14(15)21(2)18(16)24/h4-11,23H,3H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C19H17ClN2O3
Molecular Weight	356.803
Charge	0
Count

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

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002546/WC500171788.pdf
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/27089834 | https://www.vidal.ru/drugs/nerventra__40726

Laquinimod is a new orally available carboxamide derivative, which is currently developed for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases. The mechanism of action of laquinimod is not fully elucidated because the molecular target is not known. Treatment with laquinimod led to a significant and persistent increase in brain-derived neuroprotective factor (BDNF) serum levels compared to placebo treatment. In human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured. After commercial launch the unexpected severe cardiac adverse events (AEs) such as serositis, pericarditis, and myocardial infarction were detected.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15764719	Substrate 661
inflammatory response 47 Target ID: GO:0006954 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27042003 / https://www.ncbi.nlm.nih.gov/pubmed/27089834	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Relapsing-remitting multiple sclerosis 10 Sources: https://www.vidal.ru/drugs/nerventra__40726	Primary	Approved 8429	Nerventra Approved Use http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002546/WC500171788.pdf Launch Date 1.37289597E12
Crohn's disease 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25281416	Primary	Phase II 1132	Unknown Approved Use Unknown
Huntington's disease 24 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27296315	Primary	Phase II 1132	Unknown Approved Use Unknown
Lupus nephritis 6 Sources: DOI: 10.1136/annrheumdis-2013-eular.528	Primary	Phase II 1132	Unknown Approved Use Unknown
Lupus arthritis 2 Sources: https://www.google.ch/patents/US20130184310	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Suppression of experimental autoimmune neuritis by ABR-215062 is associated with altered Th1/Th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue.	2002 Apr	11985832
[Future possibilities of the multiple sclerosis treatment].	2005	16279429
Gateways to clinical trials.	2005 Jun	16082422
Determination of the immunomodulator laquinimod in human plasma by liquid chromatography/tandem mass spectrometry; development, validation and application of two methods in clinical pharmacokinetic profiling.	2006	17044118
Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-beta k.o. and wild type mice.	2006 Apr	16472873
Synthesis and reactivity of laquinimod, a quinoline-3-carboxamide: intramolecular transfer of the enol proton to a nitrogen atom as a plausible mechanism for ketene formation.	2006 Feb 17	16468821
Oral disease-modifying treatments for multiple sclerosis: the story so far.	2007	17521228
Laquinimod, a new oral drug for multiple sclerosis.	2008 Jun 21	18572062
Kynurenine pathway metabolites in humans: disease and healthy States.	2009	22084578
Review of teriflunomide and its potential in the treatment of multiple sclerosis.	2009	19557143
Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides.	2009 Apr 28	19402754
New oral drugs for multiple sclerosis.	2009 Oct	19882371
Multiple sclerosis: a supplement on the disease state, current therapies, and investigational treatments.	2010 Apr	21507801
A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells.	2010 Feb 2	20126401
Emerging multiple sclerosis oral therapies.	2010 Jan 5	20038763
Laquinimod, a new oral autoimmune modulator for the treatment of relapsing-remitting multiple sclerosis.	2010 May	20419604
New approaches in the management of multiple sclerosis.	2010 Nov 24	21151622
Emerging oral agents for multiple sclerosis.	2010 Sep	20873946
Emerging oral treatments in multiple sclerosis - clinical utility of cladribine tablets.	2010 Sep 7	20856685

Patents

Sample Use Guides

In Vivo Use Guide

0.6 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Laquinimod, at concentrations of 5 to 3000 M, was incubated for 20 min with human liver microsomes. The metabolite formation exhibited, in general, single-enzyme Michaelis-Menten kinetics with Km in the range 0.09 to 1.9 mM and Vmax from 22 to 120 pmol/mg/min.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:39:21 UTC 2023` Edited by `admin` on `Sat Dec 16 17:39:21 UTC 2023`
Record UNII	908SY76S4G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LAQUINIMOD

Official Name

English

TV-5600 FREE ACID

Code

English

LAQUINIMOD [MI]

Common Name

English

ABR-215062

Code

English

Laquinimod [WHO-DD]

Common Name

English

ABR-215062 FREE ACID

Code

English

laquinimod [INN]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

NERVENTRA (REFUSED: MULTIPLE SCLEROSIS)