Identification
- Summary
Diacerein is an slow-onset anthraquinone IL-1 inhibitor used in the treatment of degenerative joint diseases like osteoarthritis.
- Generic Name
- Diacerein
- DrugBank Accession Number
- DB11994
- Background
Diacerein is a prodrug which is metabolized to rhein. It is currently approved in France for the treatment of osteoarthritis although the use of diacerein is restricted due to the side effects including severe diarrhea 6. Diacerein is under investigation for the treatment of Insulin Resistance, Diabetes Mellitus (Type 2), and Diabetes-Related Complications.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Diacerein (DB11994)
- Weight
- Average: 368.297
Monoisotopic: 368.053217346 - Chemical Formula
- C19H12O8
- Synonyms
- Diacerein
- Diacereína
- External IDs
- AC-201
- SF-277
Pharmacology
- Indication
For the treatment of osteoarthritis affecting the hip or knee 6.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Osteoarthritis in the hip joint •••••••••••• ••••••• Symptomatic treatment of Osteoarthritis of the knee •••••••••••• ••••••• - Contraindications & Blackbox Warnings
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Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity 3 4 5.
- Mechanism of action
Diacerein's active metabolite rhein Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs 5. The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation 4. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism 3.
Target Actions Organism UOxysterols receptor LXR-alpha inhibitorHumans UOxysterols receptor LXR-beta inhibitorHumans UArylamine N-acetyltransferase inhibitorHelicobacter pylori UArachidonate 5-lipoxygenase inhibitorHumans UCytochrome P450 1A2 inhibitorHumans UCytochrome P450 3A Subfamily inhibitorHumans UCytochrome P450 2E1 inhibitorHumans UCytochrome P450 2C9 inhibitorHumans UCytochrome P450 2D6 inhibitorHumans - Absorption
Bioavailability of 50-60% 1. Entirely converted to the active metabolite rhein Rhein before reaching systemic circulation.
- Volume of distribution
15-60L 1.
- Protein binding
99% of rhein is bound to plasma proteins 1.
- Metabolism
Entirely converted to rhien Rhein through double deacetylation before reaching systemic circulation 1. Rhein Rhein is further metabolized to rhein glucuronide and rhein sulfate.
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- Route of elimination
37% excreted in urine and 53% in feces as estimated in rats 2.
- Half-life
4-10h 1.
- Clearance
Total CL is 1.5L/h and renal CL is 0.1L/h 1.
- Adverse Effects
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Rhein Rhein has an oral LD50 of >5000mg/kg in mice. This is equivalent to a diacerein dose of >6476mg/kg.
- 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 softwareAbrocitinib The metabolism of Abrocitinib can be decreased when combined with Diacerein. Acebutolol The metabolism of Acebutolol can be decreased when combined with Diacerein. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Diacerein. Acetaminophen Diacerein may increase the hepatotoxic activities of Acetaminophen. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Diacerein. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ARTRODAR 50 MG KAPSUL, 30 ADET Diacerein (50 mg) Capsule Oral BİO-GEN İLAÇ SAN.TİC.LTD. ŞTİ. 2020-08-14 Not applicable Turkey 
Categories
- ATC Codes
- M01AX21 — Diacerein
- Drug Categories
- Anthracenes
- Anti-Inflammatory Agents
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Musculo-Skeletal System
- Quinones
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as anthracenecarboxylic acids. These are organic compounds containing a carboxylic acid group attached to an anthracene ring system.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Anthracenes
- Sub Class
- Anthracenecarboxylic acids and derivatives
- Direct Parent
- Anthracenecarboxylic acids
- Alternative Parents
- Anthraquinones / Naphthalenecarboxylic acids / Tricarboxylic acids and derivatives / Aryl ketones / Carboxylic acid esters / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
- Substituents
- 2-naphthalenecarboxylic acid / 2-naphthalenecarboxylic acid or derivatives / 9,10-anthraquinone / Anthracene carboxylic acid / Anthraquinone / Aromatic homopolycyclic compound / Aryl ketone / Carbonyl group / Carboxylic acid / Carboxylic acid derivative
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 4HU6J11EL5
- CAS number
- 13739-02-1
- InChI Key
- TYNLGDBUJLVSMA-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H12O8/c1-8(20)26-13-5-3-4-11-15(13)18(23)16-12(17(11)22)6-10(19(24)25)7-14(16)27-9(2)21/h3-7H,1-2H3,(H,24,25)
- IUPAC Name
- 4,5-bis(acetyloxy)-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid
- SMILES
- CC(=O)OC1=CC=CC2=C1C(=O)C1=C(OC(C)=O)C=C(C=C1C2=O)C(O)=O
References
- General References
- Nicolas P, Tod M, Padoin C, Petitjean O: Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. [Article]
- De Witte P, Lemli J: Excretion and distribution of [14C]rhein and [14C]rhein anthrone in rat. J Pharm Pharmacol. 1988 Sep;40(9):652-5. [Article]
- Pelletier JP, Lajeunesse D, Reboul P, Mineau F, Fernandes JC, Sabouret P, Martel-Pelletier J: Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone. J Rheumatol. 2001 Apr;28(4):814-24. [Article]
- Moldovan F, Pelletier JP, Jolicoeur FC, Cloutier JM, Martel-Pelletier J: Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthritis Cartilage. 2000 May;8(3):186-96. [Article]
- Tamura T, Kosaka N, Ishiwa J, Sato T, Nagase H, Ito A: Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit articular chondrocytes. Osteoarthritis Cartilage. 2001 Apr;9(3):257-63. [Article]
- WHO Diacerein: Restricted Use [Link]
- BASG Product Information: Verboril (diacerein) oral capsules [Link]
- External Links
- PubChem Compound
- 26248
- PubChem Substance
- 347828314
- ChemSpider
- 24456
- BindingDB
- 32018
- 22759
- ChEBI
- 94708
- ChEMBL
- CHEMBL41286
- ZINC
- ZINC000003812842
- Wikipedia
- Diacerein
- MSDS
- Download (25.1 KB)
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 4 Completed Treatment Diacerein / Glucosamine / Osteoarthritis (OA) 1 4 Completed Treatment Osteoarthritis (OA) 1 4 Completed Treatment Osteoarthritis (OA) / Osteoarthritis of the Knee 1 4 Completed Treatment Osteoarthritis of the Knee 2 4 Completed Treatment Primary Gout 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, coated Oral 50 mg Capsule, coated Oral 5000000 mg Capsule Oral 50 mg Capsule Oral Tablet Oral Capsule Oral Capsule Oral 50.000 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0407 mg/mL ALOGPS logP 2.14 ALOGPS logP 1.79 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 3.37 Chemaxon pKa (Strongest Basic) -6.8 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 124.04 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 90.67 m3·mol-1 Chemaxon Polarizability 35.37 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9003000000-d062f99aea1e0899e82e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0091000000-1e60a01c2350401ab005 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00ai-0079000000-891d388baba4cf4d4ec6 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-052r-0079000000-998abc0965dca68e2338 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0193000000-7a99eb4b1fd676711128 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0091000000-5ee040e4d269e799455b 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]- 199.5836176 predictedDarkChem Lite v0.1.0 [M-H]- 197.6080176 predictedDarkChem Lite v0.1.0 [M-H]- 174.71825 predictedDeepCCS 1.0 (2019) [M+H]+ 204.7376176 predictedDarkChem Lite v0.1.0 [M+H]+ 197.1854176 predictedDarkChem Lite v0.1.0 [M+H]+ 177.07625 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.8936176 predictedDarkChem Lite v0.1.0 [M+Na]+ 197.9410176 predictedDarkChem Lite v0.1.0 [M+Na]+ 183.91237 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by L...
- Gene Name
- NR1H3
- Uniprot ID
- Q13133
- Uniprot Name
- Oxysterols receptor LXR-alpha
- Molecular Weight
- 50395.34 Da
References
- Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake t...
- Gene Name
- NR1H2
- Uniprot ID
- P55055
- Uniprot Name
- Oxysterols receptor LXR-beta
- Molecular Weight
- 50973.375 Da
References
- Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [Article]
3. Arylamine N-acetyltransferase
Unknown
Inhibitor
References
- Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS, Wu LT, Chang SH, Ho CC, Hung CF: Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J Appl Toxicol. 1998 Mar-Apr;18(2):117-23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Singh B, Nadkarni JR, Vishwakarma RA, Bharate SB, Nivsarkar M, Anandjiwala S: The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. J Ethnopharmacol. 2012 May 7;141(1):469-73. doi: 10.1016/j.jep.2012.03.012. Epub 2012 Mar 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-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 performs a variety of oxidation react...
Components:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
Drug created at October 20, 2016 21:09 / Updated at May 21, 2021 10:22