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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:: 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

PubMed

PubMed

TitleDatePubMed
In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: suppression of collagenase 1 and interleukin-1beta synthesis.
2001 Oct
[Double blockade should protect the stomach. New approach to rheumatism].
2001 Sep 20
Licofelone (ML-3000), a dual inhibitor of 5-lipoxygenase and cyclooxygenase, reduces the level of cartilage chondrocyte death in vivo in experimental dog osteoarthritis: inhibition of pro-apoptotic factors.
2002 Jul
Study of the role of leukotriene B()4 in abnormal function of human subchondral osteoarthritis osteoblasts: effects of cyclooxygenase and/or 5-lipoxygenase inhibition.
2002 Jul
The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2.
2002 Mar
Gateways to clinical trials.
2002 Oct
Licofelone, a dual lipoxygenase-cyclooxygenase inhibitor, downregulates polymorphonuclear leukocyte and platelet function.
2002 Oct 18
Licofelone (Merckle).
2003 Aug
The metabolic effects of inhibitors of 5-lipoxygenase and of cyclooxygenase 1 and 2 are an advancement in the efficacy and safety of anti-inflammatory therapy.
2003 Jul
International Conference on Inflammopharmacology -- VIII Side-Effects of Anti-inflammatory Drugs Symposium.
2003 Jul
Anti arthritic drugs--SMi conference: dual inhibitors. 28-29 April 2003, London, UK.
2003 Jun
Relative contribution of acetylated cyclo-oxygenase (COX)-2 and 5-lipooxygenase (LOX) in regulating gastric mucosal integrity and adaptation to aspirin.
2003 Jun
COX-LOX inhibition: current evidence for an emerging new therapy.
2003 May
Regulation of the expression of 5-lipoxygenase-activating protein/5-lipoxygenase and the synthesis of leukotriene B(4) in osteoarthritic chondrocytes: role of transforming growth factor beta and eicosanoids.
2004 Dec
Safety of anti-inflammatory treatment--new ways of thinking.
2004 Feb
Is licofelone, a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase, a promising alternative in anti-inflammatory therapy?
2004 Feb
The protective effect of licofelone on experimental osteoarthritis is correlated with the downregulation of gene expression and protein synthesis of several major cartilage catabolic factors: MMP-13, cathepsin K and aggrecanases.
2005
The regulation of human MMP-13 by licofelone, an inhibitor of cyclo-oxygenases and 5-lipoxygenase, in human osteoarthritic chondrocytes is mediated by the inhibition of the p38 MAP kinase signalling pathway.
2005 Jun
Effects on primary haemostasis of an anti-inflammatory agent with 5-lipoxygenase and cyclooxygenase inhibitory activity.
2006 Dec
Anti-inflammatory effect of licofelone against various inflammatory challenges.
2006 Feb
Licofelone reduces progression of structural changes in a canine model of osteoarthritis under curative conditions: effect on protease expression and activity.
2006 Jun
DMOAD developments: present and future.
2007
Licofelone--a novel analgesic and anti-inflammatory agent.
2007
Efficacy of licofelone in dogs with clinical osteoarthritis.
2007 Apr 28
Comparative protection against liver inflammation and fibrosis by a selective cyclooxygenase-2 inhibitor and a nonredox-type 5-lipoxygenase inhibitor.
2007 Dec
Selection of reliable reference genes for qPCR studies on chondroprotective action.
2007 Feb 26
Dynamic simulations on the arachidonic acid metabolic network.
2007 Mar 23
Analysis of the precision and sensitivity to change of different approaches to assess cartilage loss by quantitative MRI in a longitudinal multicentre clinical trial in patients with knee osteoarthritis.
2008
Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling.
2008
Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors.
2008 Feb
Licofelone: the answer to unmet needs in osteoarthritis therapy?
2008 Jan
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
Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1.
2008 Sep
Systematic review of the management of canine osteoarthritis.
2009 Apr 4
An exploration of the ability of tepoxalin to ameliorate the degradation of articular cartilage in a canine in vitro model.
2009 Jul 22
Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI.
2009 Jun
5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.
2010
Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis.
2010
High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes.
2010
Regulation of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase-activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic chondrocytes.
2010
Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells.
2010 Nov 17
Licofelone attenuates MPTP-induced neuronal toxicity: behavioral, biochemical and cellular evidence.
2010 Oct
Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice.
2010 Sep
Investigational pharmacology for low back pain.
2010 Sep 6
Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase.
2011 Apr 28
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
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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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