LICOFELONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H22ClNO2
Molecular Weight	379.879
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)CN2C(CC(O)=O)=C(C(=C2C1)C3=CC=CC=C3)C4=CC=C(Cl)C=C4

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	379.879
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800003927
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17305568	Inhibitor 8504		0.21 µM [IC50]
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17305568	Inhibitor 8504		0.18 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 157 Sources: http://adisinsight.springer.com/drugs/800003927	Primary	Phase III 665	Unknown Approved Use Unknown
Rheumatoid arthritis 320 Sources: http://adisinsight.springer.com/drugs/800003927	Primary	Preclinical	Unknown Approved Use Unknown
Pain 619 Sources: http://adisinsight.springer.com/drugs/800003927	Primary	Phase II 1147	Unknown Approved Use Unknown
Inflammation 105 Sources: http://adisinsight.springer.com/drugs/800003927	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1665 ng/mL REVIEW http://ijpt.iums.ac.ir/article-1-226-en.html	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		LICOFELONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1727 ng/mL REVIEW http://ijpt.iums.ac.ir/article-1-226-en.html	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LICOFELONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4582 ng × h/mL REVIEW http://ijpt.iums.ac.ir/article-1-226-en.html	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		LICOFELONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.1 h REVIEW http://ijpt.iums.ac.ir/article-1-226-en.html	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		LICOFELONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	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: https://pubmed.ncbi.nlm.nih.gov/15089890

AEs

AE	Significance	Dose	Population
Flatulence	13.3%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
coughing	13.3%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
rhinitis	16.6%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
abdominal pain	26.7%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
diarrhea	50%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
dizzines	6.7%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
fever	6.7%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890
hot flashes	6.7%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15089890	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15089890

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001PID	https://www.1pchem.com/search?query=1P001PID
AK Scientific	B699	https://aksci.com/item_detail.php?cat=B699
Angene	AGN-PC-07Y4OS	http://www.angenechemical.com/productshow/AGN-PC-07Y4OS.html
AOBIOUS INC	AOB3889	http://aobious.com/aobious/search?search_query=AOB3889
ApexBio Technology	B1448	https://www.apexbt.com/catalogsearch/result/?q=B1448
AstaTech	C14938	http://astatechinc.com/CPSResult.php?CRNO=C14938
BLD Pharm	BD305628	http://www.bldpharm.com/search/Search.html?keyword=BD305628
BOC Sciences	156897-06-2	http://www.bocsci.com/description.asp?cas=156897-06-2
Cayman Chemical	10007692	http://www.caymanchem.com/app/template/Product.vm/catalog/10007692
Chem Scene	CS-0013159	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0013159
eMolecules	6697560	https://orderbb.emolecules.com/search/#?query=6697560
eNovation Chemicals	D491447	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D491447&searchbtn.x=0&searchbtn.y=0
Hairui	HR105071	http://www.hairuichem.com/en/product/search.do?q=HR105071
KeyOrganics	AS-73938	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-73938
Lab Network	LN01287863	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01287863
Lab Seeker	SC-20109	http://www.labseeker.com/search.php?keywords=SC-20109&category=0
LabSeeker	SC-20109	http://www.labseeker.com/search.php?keywords=SC-20109&category=0
mcule	MCULE-5104424173	https://mcule.com/MCULE-5104424173/
MedChem Express	HY-B1452	https://www.medchemexpress.com/search.html?q=HY-B1452&ft=&fa=&fp=
MolPort	MolPort-006-169-990	https://www.molport.com/shop/molecule-link/MolPort-006-169-990
MuseChem	R009348	https://www.musechem.com/product/R009348.html
ShangHai Biochempartner	BCP06598	http://www.biochempartner.com/search_BCP06598
Toronto Research Chemicals	L397730	https://www.trc-canada.com/product-detail/?CatNum=L397730

PubMed

Title	Date	PubMed
Chemopreventive efficacy and mechanism of licofelone in a mouse lung tumor model via aspiration.	2011-08	21562034
Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase.	2011-04-28	21434686
Relationship between bone marrow lesions, cartilage loss and pain in knee osteoarthritis: results from a randomised controlled clinical trial using MRI.	2010-12	20610445
Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis.	2010-12	20570834
Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells.	2010-11-17	21080973
Licofelone attenuates MPTP-induced neuronal toxicity: behavioral, biochemical and cellular evidence.	2010-10	20697819
Investigational pharmacology for low back pain.	2010-09-06	21197321
Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice.	2010-09	20684827
5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.	2010	21833182
Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis.	2010	20923566
High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes.	2010	20799933
Regulation of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase-activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic chondrocytes.	2010	20144213
An exploration of the ability of tepoxalin to ameliorate the degradation of articular cartilage in a canine in vitro model.	2009-07-22	19624842
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.	2009-06	18653484
Systematic review of the management of canine osteoarthritis.	2009-04-04	19346540
Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes.	2009	19664212
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	19291317
The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer.	2008-12	19707453
Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1.	2008-09	18550688
Is collagenase-3 (MMP-13) expression in chondrosarcoma of the jaws a true marker for tumor aggressiveness?	2008-06-13	18554405
In vitro metabolism of 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid (licofelone, ML3000), an inhibitor of cyclooxygenase-1 and -2 and 5-lipoxygenase.	2008-05	18268076
Gateways to clinical trials.	2008-04-05	18389098
The dual inhibitor of lipoxygenase and cyclooxygenase ML3000 decreases the expression of CXCR3 ligands.	2008-04	17666446
Gateways to clinical trials.	2008-03	18560631
A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models.	2008-02-12	18269731
Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors.	2008-02	18280718
Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade.	2008-02	18033773
Licofelone: the answer to unmet needs in osteoarthritis therapy?	2008-01	18457611
Combination Therapy of PPARgamma Ligands and Inhibitors of Arachidonic Acid in Lung Cancer.	2008	19277204
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	18986534
Finding multiple target optimal intervention in disease-related molecular network.	2008	18985027
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	18578867
Comparative protection against liver inflammation and fibrosis by a selective cyclooxygenase-2 inhibitor and a nonredox-type 5-lipoxygenase inhibitor.	2007-12	17766677
The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products.	2007-10	17704828
Anticancer effects of licofelone (ML-3000) in prostate cancer cells.	2007-08-19	17695530
Gastrointestinal safety of novel nonsteroidal antiinflammatory drugs: selective COX-2 inhibitors and beyond.	2007-08	17933277
Efficacy of licofelone in dogs with clinical osteoarthritis.	2007-04-28	17468321
Dynamic simulations on the arachidonic acid metabolic network.	2007-03-23	17381237
Selection of reliable reference genes for qPCR studies on chondroprotective action.	2007-02-26	17324259
Arthritis clinical trial results revealed.	2007-01-03	17200465
Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis.	2007-01	17015640
Activity and potential role of licofelone in the management of osteoarthritis.	2007	18044077
Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study.	2007	18031579
DMOAD developments: present and future.	2007	17922676
Extracellular localization of galectin-3 has a deleterious role in joint tissues.	2007	17326835
Licofelone--a novel analgesic and anti-inflammatory agent.	2007	17305568
Effects on primary haemostasis of an anti-inflammatory agent with 5-lipoxygenase and cyclooxygenase inhibitory activity.	2006-12	17122671
The lipoxygenase-cyclooxygenase inhibitor licofelone prevents thromboxane A2-mediated cardiovascular derangement triggered by the inflammatory peptide fMLP in the rabbit.	2006-09-28	16920097
Licofelone reduces progression of structural changes in a canine model of osteoarthritis under curative conditions: effect on protease expression and activity.	2006-06	16652435
Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow.	2006	16569256

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 18:03:19 GMT 2025` Edited by `admin` on `Mon Mar 31 18:03:19 GMT 2025`
Record UNII	P5T6BYS22Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LICOFELONE

Official Name

English

LICOFELONE [MI]

Preferred 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

Classification Tree Code System Code

NCI_THESAURUS

C1323