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
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)
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 |
DescriptionSources: http://adisinsight.springer.com/drugs/800003927Curator'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
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
Sources: http://hktmc.com.cn/ChineseMedia/Magazine/Medicine/ajdmpk/AJDMPK-2010-4/AJPP%202010-4%20_287-299_%20ML3000.pdf
Curator's Comment:: Almost no penetration of the blood-brain barrier was noted in animal study. No human data available.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17305568 |
0.21 µM [IC50] | ||
Target ID: CHEMBL215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17305568 |
0.18 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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%) Sources: hot flashes (6.7%) dizzines (6.7%) abdominal pain (26.7%) diarrhea (50%) Flatulence (13.3%) coughing (13.3%) rhinitis (16.6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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Gateways to clinical trials. | 2004 Sep |
|
Leukotriene and prostaglandin synthesis pathways in osteoarthritic synovial membranes: regulating factors for interleukin 1beta synthesis. | 2005 Apr |
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Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a COX-2 selective inhibitor, in dogs. | 2005 Feb |
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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 |
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Eicosanoids, osteoarthritis, and crystal deposition diseases. | 2005 May |
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Efficacy of licofelone in dogs with clinical osteoarthritis. | 2007 Apr 28 |
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Anticancer effects of licofelone (ML-3000) in prostate cancer cells. | 2007 Jul-Aug |
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Dynamic simulations on the arachidonic acid metabolic network. | 2007 Mar 23 |
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The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products. | 2007 Oct |
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Finding multiple target optimal intervention in disease-related molecular network. | 2008 |
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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 |
Sample Use Guides
In Vivo Use Guide
Sources: http://adisinsight.springer.com/drugs/800003927
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12005204
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
Edited
Sat Jun 26 02:40:52 UTC 2021
by
admin
on
Sat Jun 26 02:40:52 UTC 2021
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Record UNII |
P5T6BYS22Y
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C1323
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156897-06-2
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C088092
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M6803
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P5T6BYS22Y
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7786
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DB04725
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LICOFELONE
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133021
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CHEMBL300982
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SUB33729
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156897-06-2
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C63957
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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