ROQUINIMEX

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H16N2O3
Molecular Weight	308.3312
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C(=O)C1=C(O)C2=C(C=CC=C2)N(C)C1=O)C3=CC=CC=C3

InChI

InChIKey=SGOOQMRIPALTEL-UHFFFAOYSA-N

InChI=1S/C18H16N2O3/c1-19(12-8-4-3-5-9-12)17(22)15-16(21)13-10-6-7-11-14(13)20(2)18(15)23/h3-11,21H,1-2H3

HIDE SMILES / InChI

Molecular Formula	C18H16N2O3
Molecular Weight	308.3312
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/11407306 | http://adisinsight.springer.com/drugs/800001478 | https://www.ncbi.nlm.nih.gov/pubmed/10773855

Roquinimex (Linomide, LS 2616) is a quinoline-3-carboxamide with pleiotropic immune modulating capacity and it has therapeutic effects in several experimental animal models of autoimmune diseases. Linomide has been evaluated in clinical trials for multiple sclerosis, and was indeed shown to have disease inhibitory effects. However, due to unexpected side effects recorded in patients treated with Linomide, premature termination of clinical trials was required. The basic mechanism(s) of action of Linomide in inducing beneficial effects in autoimmune diseases is still elusive. Some experimental evidence indicates that Linomide influences the regulation of the cytokine profile, resulting in the inhibition of autoimmune and inflammation pathologies. Roquinimex possesses potential antineoplastic activity. Roquinimex inhibits endothelial cell proliferation, migration, and basement membrane invasion; reduces the secretion of the angiogenic factor tumor necrosis factor alpha by tumor-associated macrophages (TAMs); and inhibits angiogenesis. Roquinimex was in phase III clinical trials with Pharmacia Corporation in Europe and the US for the treatment of multiple sclerosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
T cell cytokine production 5 Target ID: GO:0002369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369127	Modulator 846
angiogenesis 17 Target ID: GO:0001525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12643940 \| http://adisinsight.springer.com/drugs/800001478 \| https://www.ncbi.nlm.nih.gov/pubmed/9643647	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Multiple sclerosis 107 Sources: http://adisinsight.springer.com/drugs/800001478	Primary	Phase III 665	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: http://adisinsight.springer.com/drugs/800001478 https://www.thepharmaletter.com/article/kabi-s-linomide-in-phase-iii-for-aml	Primary	Phase III 665	Unknown Approved Use Unknown
Gastrointestinal cancer 3 Sources: http://adisinsight.springer.com/drugs/800001478	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9171853/	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9171853/	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10760843/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROQUINIMEX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse events
7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	Disc. AE: Myocardial infarction, Pulmonary embolism... Other AEs: Bursitis, Peripheral edema... AEs leading to discontinuation/dose reduction: Myocardial infarction (grade 5, 0.6%) Pulmonary embolism (grade 5, 0.6%) Myocardial infarction (grade 3, 0.6%) Pleuropericarditis (4%) Pleural effusion (grade 3, 2.4%) Other AEs: Bursitis (9.2%) Peripheral edema (19%) Arthralgia (17%) Myalgia (28%) Facial edema (21%) Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/

AEs

AE	Significance	Dose	Population
Arthralgia	17%	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Peripheral edema	19%	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Facial edema	21%	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Myalgia	28%	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Pleuropericarditis	4% Disc. AE	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Bursitis	9.2%	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Myocardial infarction	grade 3, 0.6% Disc. AE	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Pleural effusion	grade 3, 2.4% Disc. AE	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Myocardial infarction	grade 5, 0.6% Disc. AE	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/
Pulmonary embolism	grade 5, 0.6% Disc. AE	7.5 mg 1 times / day multiple, oral Highest studied dose Dose: 7.5 mg, 1 times / day Route: oral Route: multiple Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10802775/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087 substrate 1946	inhibitor 2438 substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 MRP3 246 BSEP 550 MRP4 290 MRP2 499 CYP19A1 429	P-gp 2052 CYP2C19 1119 CYP1A2 1197 CYP2A6 626 CYP2E1 729

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/54676478#section=Biological-Test-Results Page: 3.0	inconclusive [EC50 15.8489 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE2NzIifX0=	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTE2NzIifX0=	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExNjcyIn19	no [IC50 >133 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/54676478#section=Biological-Test-Results Page: 76.0	no

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	likely
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	major
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	minor
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/54676478#section=Biological-Test-Results Page: 120 \| 121	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	weak
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	weak
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	weak
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11055268/	weak

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/54676478#section=Biological-Test-Results Page: 134.0

PubMed

Title	Date	PubMed
H1521, a novel derivative of 4-hydroxyquinoline-3-carboxamide, suppresses the development of lupus in mice by inducing Th1 cytokine profile in T cells.	2011-04	21195814
Immunomodulation by roquinimex decreases the expression of IL-23 (p19) mRNA in the brains of herpes simplex virus type 1 infected BALB/c mice.	2004-08	15270847

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of multiple sclerosis: 2.5 or 5 mg. The target treatment consisted of Linomide 2 x 2.5 mg daily, administered orally as tablets for the planned treatment period of 36 months. All patients started with one tablet daily (i.e. 2.5 mg Linomide or placebo) and if this dose was well tolerated, it was to be changed into a 5 mg dose after 3 months of treatment.

Route of Administration: Oral

In Vitro Use Guide

Linomide (50-200 ug/ml) was not cytotoxic in vitro on resting capillary endothelial cells but blocked endothelial cell replication induced by VEGF.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:46:05 GMT 2025` Edited by `admin` on `Mon Mar 31 18:46:05 GMT 2025`
Record UNII	372T2944C0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FCF 89

Preferred Name

English

ROQUINIMEX

Official Name

English

roquinimex [INN]

Common Name

English

Roquinimex [WHO-DD]

Common Name

English

ROQUINIMEX [MI]

Common Name

English

LS-2616

Code

English

3-QUINOLINECARBOXAMIDE, 1,2-DIHYDRO-4-HYDROXY-N,1-DIMETHYL-2-OXO-N-PHENYL

Common Name

English

LS 2616

Code

English

ROQUINIMEX [USAN]

Common Name

English

FCF-89

Code

English

1,2-Dihydro-4-hydroxy-N,1-dimethyl-2-oxo-3-quinolinecarboxanilide

Systematic Name

English

ROQUINIMEX [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

72893