Identification
- Generic Name
- Licofelone
- DrugBank Accession Number
- DB04725
- Background
Developed by the German pharmaceutical company, Merckle GmbH, together with EuroAlliance partners Alfa Wassermann and Lacer, licofelone (ML3000) is a dual COX/LOX inhibitor and the first member of this new class of analgesic and anti-inflammatory drugs. It is currently under evaluation as a treatment for osteoarthritis (OA), the most common form of arthritis. Although phase III trials have been successfully completed in OA patients no dates for regulatory submission have yet been given.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Licofelone (DB04725)
- Weight
- Average: 379.879
Monoisotopic: 379.13390666 - Chemical Formula
- C23H22ClNO2
- Synonyms
- Licofelone
- External IDs
- ML 3000
- ML-3000
- ML3000
Pharmacology
- Indication
For the management of osteoarthritis.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Licofelone belongs to a novel class of dual-acting anti-inflammatory drugs called COX/LO inhibitors. This group of drugs simultaneously inhibits the enzymes cyclooxygenase (COX) and 5-lipoxygenase (LO).
- Mechanism of action
Licofelone, through combined 5-LOX/COX-inhibition, reduces levels of inflammatory prostaglandins and leukotrienes.
Target Actions Organism UArachidonate 5-lipoxygenase Not Available Humans UProstaglandin G/H synthase 2 Not Available Humans UGroup IIE secretory phospholipase A2 Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Licofelone can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Licofelone is combined with Abciximab. Abiraterone The metabolism of Licofelone can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Licofelone. Acebutolol Licofelone may decrease the antihypertensive activities of Acebutolol. - Food Interactions
- Not Available
Categories
- Drug Categories
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antirheumatic Agents
- Central Nervous System Agents
- Cyclooxygenase Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Lipoxygenase Inhibitors
- Peripheral Nervous System Agents
- Sensory System Agents
- UGT1A3 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylpyrroles. These are aromatic heterocyclic compounds with a structure based on a pyrrole ring linked to exactly two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrroles
- Sub Class
- Substituted pyrroles
- Direct Parent
- Diphenylpyrroles
- Alternative Parents
- Pyrrolizines / Chlorobenzenes / Aryl chlorides / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides show 3 more
- Substituents
- 3,4-diphenylpyrrole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Chlorobenzene show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- P5T6BYS22Y
- CAS number
- 156897-06-2
- InChI Key
- UAWXGRJVZSAUSZ-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid
- SMILES
- CC1(C)CN2C(CC(O)=O)=C(C(=C2C1)C1=CC=CC=C1)C1=CC=C(Cl)C=C1
References
- General References
- Narayanan NK, Nargi D, Attur M, Abramson SB, Narayanan BA: Anticancer effects of licofelone (ML-3000) in prostate cancer cells. Anticancer Res. 2007 Jul-Aug;27(4B):2393-402. [Article]
- Kulkarni SK, Singh VP: Licofelone--a novel analgesic and anti-inflammatory agent. Curr Top Med Chem. 2007;7(3):251-63. [Article]
- External Links
- PubChem Compound
- 133021
- PubChem Substance
- 175426859
- ChemSpider
- 117391
- BindingDB
- 50038649
- ChEMBL
- CHEMBL300982
- ZINC
- ZINC000003805769
- PDBe Ligand
- LCF
- Wikipedia
- Licofelone
- PDB Entries
- 1zyx / 4g8h
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00111 mg/mL ALOGPS logP 5.39 ALOGPS logP 5.72 Chemaxon logS -5.5 ALOGPS pKa (Strongest Acidic) 4.8 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 42.23 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 108.79 m3·mol-1 Chemaxon Polarizability 41.8 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9088 Caco-2 permeable + 0.5558 P-glycoprotein substrate Non-substrate 0.522 P-glycoprotein inhibitor I Non-inhibitor 0.7895 P-glycoprotein inhibitor II Non-inhibitor 0.5081 Renal organic cation transporter Non-inhibitor 0.7022 CYP450 2C9 substrate Non-substrate 0.7715 CYP450 2D6 substrate Non-substrate 0.7635 CYP450 3A4 substrate Substrate 0.7167 CYP450 1A2 substrate Inhibitor 0.5308 CYP450 2C9 inhibitor Non-inhibitor 0.6777 CYP450 2D6 inhibitor Non-inhibitor 0.8277 CYP450 2C19 inhibitor Inhibitor 0.5281 CYP450 3A4 inhibitor Non-inhibitor 0.9103 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6807 Ames test Non AMES toxic 0.7968 Carcinogenicity Non-carcinogens 0.6973 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6966 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9775 hERG inhibition (predictor II) Non-inhibitor 0.6155
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-47bd454884c9f9f82313 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-0009000000-8a844ccc18a7c7e8b9cf Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-0009000000-c393ef534560e57c2edc Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-02474ab24844ed7bfe4c Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01x9-0259000000-513994b3393003431a4e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-02u0-7962000000-21740e19da9346f8513b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 182.52277 predictedDeepCCS 1.0 (2019) [M+H]+ 184.88078 predictedDeepCCS 1.0 (2019) [M+Na]+ 191.87202 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Iron ion binding
- Specific Function
- Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
- Gene Name
- ALOX5
- Uniprot ID
- P09917
- Uniprot Name
- Arachidonate 5-lipoxygenase
- Molecular Weight
- 77982.595 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Vidal C, Gomez-Hernandez A, Sanchez-Galan E, Gonzalez A, Ortega L, Gomez-Gerique JA, Tunon J, Egido J: Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. J Pharmacol Exp Ther. 2007 Jan;320(1):108-16. Epub 2006 Oct 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Vidal C, Gomez-Hernandez A, Sanchez-Galan E, Gonzalez A, Ortega L, Gomez-Gerique JA, Tunon J, Egido J: Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. J Pharmacol Exp Ther. 2007 Jan;320(1):108-16. Epub 2006 Oct 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phospholipase a2 activity
- Specific Function
- PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids.
- Gene Name
- PLA2G2E
- Uniprot ID
- Q9NZK7
- Uniprot Name
- Group IIE secretory phospholipase A2
- Molecular Weight
- 15988.525 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Albrecht W, Unger A, Nussler AK, Laufer S: 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. Drug Metab Dispos. 2008 May;36(5):894-903. doi: 10.1124/dmd.108.020347. Epub 2008 Feb 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Drug created at September 11, 2007 17:49 / Updated at February 21, 2021 18:51