This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Laquinimod
Accession Number
DB06685
Type
Small Molecule
Groups
Investigational
Description

Laquinimod is an immunomodulator developed by Active Biotech and produced by Teva Pharmaceutical Industries. It is currently under development in phase III trials for treatment of multiple sclerosis as an oral therapy, like fingolimod. It has been shown to reduce disease activity on magnetic resonance imaging and to be well tolerated orally.

Structure
Thumb
Synonyms
  • SAIK-MS
External IDs
ABR-215062
Product Ingredients
IngredientUNIICASInChI Key
Laquinimod sodium4H914M0CSP248282-07-7JWHPPWBIIQMBQC-UHFFFAOYSA-M
Categories
UNII
908SY76S4G
CAS number
248281-84-7
Weight
Average: 356.81
Monoisotopic: 356.0927701
Chemical Formula
C19H17ClN2O3
InChI Key
GKWPCEFFIHSJOE-UHFFFAOYSA-N
InChI
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
IUPAC Name
5-chloro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide
SMILES
CCN(C(=O)C1=C(O)C2=C(C=CC=C2Cl)N(C)C1=O)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in multiple sclerosis.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of laquinimod.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmiodaroneThe metabolism of Laquinimod can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Laquinimod can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Laquinimod can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Laquinimod can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of Laquinimod can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Laquinimod can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Laquinimod can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Laquinimod can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Laquinimod can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Laquinimod can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Laquinimod can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Laquinimod can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Laquinimod can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Laquinimod can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Laquinimod can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Laquinimod can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Laquinimod can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Laquinimod can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Laquinimod can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Laquinimod can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Laquinimod can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of Laquinimod can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Laquinimod can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Laquinimod can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Laquinimod can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Laquinimod can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Laquinimod can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Laquinimod can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Laquinimod can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Laquinimod can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Laquinimod can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Laquinimod can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Laquinimod can be increased when it is combined with Fusidic Acid.Approved
ImatinibThe metabolism of Laquinimod can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Laquinimod can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Laquinimod can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Laquinimod can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Laquinimod can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Laquinimod can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Laquinimod can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Laquinimod can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Laquinimod can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Laquinimod can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Laquinimod can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Laquinimod can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Laquinimod can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Laquinimod can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Laquinimod can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Laquinimod can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Laquinimod can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Laquinimod can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Laquinimod can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Laquinimod can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Laquinimod can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Laquinimod can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Laquinimod can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Laquinimod can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Laquinimod can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Laquinimod can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Laquinimod can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Laquinimod can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Laquinimod can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Laquinimod can be increased when combined with Rifapentine.Approved
SaquinavirThe metabolism of Laquinimod can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Laquinimod can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Laquinimod can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Laquinimod can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Laquinimod can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Laquinimod can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Laquinimod can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Laquinimod can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Laquinimod can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Laquinimod can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Laquinimod can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Laquinimod can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Laquinimod can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Laquinimod can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Laquinimod can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Tuvesson H, Hallin I, Persson R, Sparre B, Gunnarsson PO, Seidegard J: Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of laquinimod, a novel immunomodulator. Drug Metab Dispos. 2005 Jun;33(6):866-72. Epub 2005 Mar 11. [PubMed:15764719]
  2. Comi G, Pulizzi A, Rovaris M, Abramsky O, Arbizu T, Boiko A, Gold R, Havrdova E, Komoly S, Selmaj K, Sharrack B, Filippi M: Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 2008 Jun 21;371(9630):2085-92. doi: 10.1016/S0140-6736(08)60918-6. [PubMed:18572078]
  3. Yang JS, Xu LY, Xiao BG, Hedlund G, Link H: Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats. J Neuroimmunol. 2004 Nov;156(1-2):3-9. [PubMed:15465591]
External Links
PubChem Compound
54677946
PubChem Substance
347827782
ChemSpider
11444966
ChEBI
134738
ChEMBL
CHEMBL66092
Wikipedia
Laquinimod
ATC Codes
N07XX10 — Laquinimod

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailablePharmacodynamics / Pharmacokinetics1
2Active Not RecruitingTreatmentHuntington's Disease (HD)1
2Active Not RecruitingTreatmentMultiple Sclerosis, Primary Progressive1
2CompletedTreatmentCrohn's Disease (CD)1
2CompletedTreatmentLupus Arthritis1
2CompletedTreatmentNephritis, Lupus1
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3CompletedTreatmentDisseminated Sclerosis3
3TerminatedTreatmentRelapsing Multiple Sclerosis (RMS)2
3WithdrawnTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0438 mg/mLALOGPS
logP2.77ALOGPS
logP2.55ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)5.02ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.85 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity97.31 m3·mol-1ChemAxon
Polarizability35.31 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.983
Blood Brain Barrier+0.8819
Caco-2 permeable+0.6474
P-glycoprotein substrateNon-substrate0.6369
P-glycoprotein inhibitor INon-inhibitor0.8987
P-glycoprotein inhibitor IIInhibitor0.6333
Renal organic cation transporterNon-inhibitor0.8013
CYP450 2C9 substrateNon-substrate0.7842
CYP450 2D6 substrateNon-substrate0.8278
CYP450 3A4 substrateSubstrate0.5998
CYP450 1A2 substrateNon-inhibitor0.5961
CYP450 2C9 inhibitorInhibitor0.506
CYP450 2D6 inhibitorNon-inhibitor0.8592
CYP450 2C19 inhibitorInhibitor0.5187
CYP450 3A4 inhibitorNon-inhibitor0.6712
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7445
Ames testNon AMES toxic0.6719
CarcinogenicityNon-carcinogens0.7705
BiodegradationNot ready biodegradable0.9957
Rat acute toxicity2.2971 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9702
hERG inhibition (predictor II)Non-inhibitor0.6325
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Aromatic anilides
Alternative Parents
Quinoline-3-carboxamides / Chloroquinolines / Hydroquinolones / Hydroxyquinolines / Hydroquinolines / Pyridinecarboxylic acids and derivatives / Pyridinones / Hydroxypyridines / Aryl chlorides / Tertiary carboxylic acid amides
show 11 more
Substituents
Aromatic anilide / Quinoline-3-carboxamide / Haloquinoline / Dihydroquinolone / Hydroxyquinoline / Chloroquinoline / Dihydroquinoline / Quinoline / Pyridine carboxylic acid or derivatives / Hydroxypyridine
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Tuvesson H, Hallin I, Persson R, Sparre B, Gunnarsson PO, Seidegard J: Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of laquinimod, a novel immunomodulator. Drug Metab Dispos. 2005 Jun;33(6):866-72. Epub 2005 Mar 11. [PubMed:15764719]
  2. Fernandez O: Oral laquinimod treatment in multiple sclerosis. Neurologia. 2011 Mar;26(2):111-7. doi: 10.1016/j.nrl.2010.07.027. [PubMed:21163185]

Drug created on March 19, 2008 10:49 / Updated on December 01, 2017 17:27