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Details

Stereochemistry ACHIRAL
Molecular Formula C23H22ClNO2
Molecular Weight 379.8801
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LICOFELONE

SMILES

CC1(C)Cc2c(-c3ccccc3)c(-c4ccc(cc4)Cl)c(CC(=O)O)n2C1

InChI

InChIKey=UAWXGRJVZSAUSZ-UHFFFAOYSA-N
InChI=1S/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27)

HIDE SMILES / InChI

Molecular Formula C23H22ClNO2
Molecular Weight 379.8801
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17305568 http://hktmc.com.cn/ChineseMedia/Magazine/Medicine/ajdmpk/AJDMPK-2010-4/AJPP%202010-4%20_287-299_%20ML3000.pdf

Licofelone (ML 3000) is a pyrrolizine derivative originally discovered by Merckle GmbH and developed by EuroAllaince with a unique pharmacological profile, which comprises optimal gastrointestinal tolerability and high analgesic and anti-inflammatory activity. These effects are due to balanced and selective inhibition of both cyclo-oxygenase and 5-lipoxygenase. Inhibition of 5-lipoxygenase may reduce the gastrointestinal toxicity associated with other non steroidal anti-inflammatory drugs, which only inhibit cyclooxygenase. Licofelone also has antipyretic and antiaggregatory properties. Clinical and preclinical trials were also undertaken for osteoarthritis, rheumatoid arthritis, asthma, pain and inflammation. However, development for these indications appear to have been discontinued.

CNS Activity

Curator's Comment:: Almost no penetration of the blood-brain barrier was noted in animal study. No human data available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.21 µM [IC50]
0.18 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
Other AEs: fever, hot flashes...
Other AEs:
fever (6.7%)
hot flashes (6.7%)
dizzines (6.7%)
abdominal pain (26.7%)
diarrhea (50%)
Flatulence (13.3%)
coughing (13.3%)
rhinitis (16.6%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Flatulence 13.3%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
coughing 13.3%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
rhinitis 16.6%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
abdominal pain 26.7%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
diarrhea 50%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
dizzines 6.7%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
fever 6.7%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
hot flashes 6.7%
400 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, ADULT
n = 30
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Dual inhibition of 5-lipoxygenase and cyclooxygenases 1 and 2 by ML3000 reduces joint destruction in adjuvant arthritis.
2001 Sep
[Double blockade should protect the stomach. New approach to rheumatism].
2001 Sep 20
Antithrombotic and platelet function inhibiting effects of ML3000, a new antiinflammatory drug with Cox/5-LOX inhibitory activity.
2002 Mar
Gateways to clinical trials.
2002 Oct
Gateways to clinical trials.
2003 Dec
Safety of anti-inflammatory treatment--new ways of thinking.
2004 Feb
Osteoarthritis therapy--are there still unmet needs?
2004 Feb
Inhibition of gastric H,K-ATPase activity and gastric epithelial cell IL-8 secretion by the pyrrolizine derivative ML 3000.
2004 Feb 10
The inhibition of subchondral bone resorption in the early phase of experimental dog osteoarthritis by licofelone is associated with a reduction in the synthesis of MMP-13 and cathepsin K.
2004 Mar
Gateways to clinical trials.
2004 Sep
Leukotriene and prostaglandin synthesis pathways in osteoarthritic synovial membranes: regulating factors for interleukin 1beta synthesis.
2005 Apr
Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a COX-2 selective inhibitor, in dogs.
2005 Feb
Effect of licofelone against NSAIDs-induced gastrointestinal ulceration and inflammation.
2005 Mar
Dual inhibition of cyclo-oxygenases and 5-lipoxygenase: a novel therapeutic approach to inflammation?
2005 May
Eicosanoids, osteoarthritis, and crystal deposition diseases.
2005 May
Efficacy of licofelone in dogs with clinical osteoarthritis.
2007 Apr 28
Anticancer effects of licofelone (ML-3000) in prostate cancer cells.
2007 Jul-Aug
Dynamic simulations on the arachidonic acid metabolic network.
2007 Mar 23
The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products.
2007 Oct
Finding multiple target optimal intervention in disease-related molecular network.
2008
Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors.
2008 Feb
Is collagenase-3 (MMP-13) expression in chondrosarcoma of the jaws a true marker for tumor aggressiveness?
2008 Jun 13
Gateways to clinical trials.
2008 Mar
Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
2009
Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice.
2010 Sep
Chemopreventive efficacy and mechanism of licofelone in a mouse lung tumor model via aspiration.
2011 Aug
Patents

Sample Use Guides

In a double-blind study, licofelone significantly improved the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and also pain, stiffness and disability relative to placebo in osteoarthritis patients when orally administered twice-daily at doses of 200mg and 400mg. A lower dose (100mg) was not sufficiently effective
Route of Administration: Oral
Using a human whole blood assay it was shown that 0.3-30 ug/ml licofelone (ML 3000) concentration-dependently inhibited the synthesis of PGE2 (IC50=3.9 uM) and 1-10 uM inhibited the synthesis of LTB4 in a concentration related manner (IC50=3.6 uM)
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:40:52 UTC 2021
Edited
by admin
on Sat Jun 26 02:40:52 UTC 2021
Record UNII
P5T6BYS22Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LICOFELONE
INN   MART.   MI  
INN  
Official Name English
LICOFELONE [INN]
Common Name English
ML 3000
Common Name English
(6-(4-CHLOROPHENYL)-2,2-DIMETHYL-7-PHENYL-2,3-DIHYDRO-1H-PYRROLIZINE-5-YL)-ACETIC ACID
Systematic Name English
LICOFELONE [MART.]
Common Name English
LICOFELONE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1323
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
Code System Code Type Description
EPA CompTox
156897-06-2
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
MESH
C088092
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
MERCK INDEX
M6803
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY Merck Index
FDA UNII
P5T6BYS22Y
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
INN
7786
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
DRUG BANK
DB04725
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
WIKIPEDIA
LICOFELONE
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
PUBCHEM
133021
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
ChEMBL
CHEMBL300982
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
EVMPD
SUB33729
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
CAS
156897-06-2
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
NCI_THESAURUS
C63957
Created by admin on Sat Jun 26 02:40:53 UTC 2021 , Edited by admin on Sat Jun 26 02:40:53 UTC 2021
PRIMARY
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