NAV

Diacerein

Identification

Summary

Diacereinis 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 diarrhea6. 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
 3D
Similar Structures
Weight
Average: 368.297
Monoisotopic: 368.053217346
Chemical Formula
C19H12O8
Synonyms
  • Diacerein
  • Diacereína
External IDs
  • AC-201
  • SF-277

Pharmacology

Indication

治疗骨关节炎的影响hip or knee6.

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity345.

Mechanism of action

Diacerein's active metabolite rheinRheinreduces 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 MMPs5. 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 inflammation4. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism3.

Target Actions Organism
UOxysterols receptor LXR-alpha
inhibitor
 Humans
UOxysterols receptor LXR-beta
inhibitor
 Humans
UArylamine N-acetyltransferase
inhibitor
 Helicobacter pylori
UArachidonate 5-lipoxygenase
inhibitor
 Humans
UCytochrome P450 1A2
inhibitor
 Humans
UCytochrome P450 3A Subfamily
inhibitor
 Humans
UCytochrome P450 2E1
inhibitor
 Humans
UCytochrome P450 2C9
inhibitor
 Humans
UCytochrome P450 2D6
inhibitor
 Humans
Absorption

Bioavailability of 50-60%1. Entirely converted to the active metabolite rheinRheinbefore reaching systemic circulation.

Volume of distribution

15-60L1.

Protein binding

99% of rhein is bound to plasma proteins1.

Metabolism

Entirely converted to rhienRheinthrough double deacetylation before reaching systemic circulation1. RheinRheinis 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 rats2.

Half-life

4-10h1.

Clearance

Total CL is 1.5L/h and renal CL is 0.1L/h1.

Adverse Effects
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Toxicity

RheinRheinhas an oral LD50 of >5000mg/kg in mice. This is equivalent to a diacerein dose of >6476mg/kg.

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" 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
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interactions in your software
Abrocitinib 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.
Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be decreased when combined with Diacerein.
Acyclovir The metabolism of Acyclovir can be decreased when combined with Diacerein.
Agomelatine The metabolism of Agomelatine can be decreased when combined with Diacerein.
Albendazole The metabolism of Albendazole can be decreased when combined with Diacerein.
Almotriptan The metabolism of Almotriptan can be decreased when combined with Diacerein.
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Food Interactions
Not Available

Products

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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 flag

Categories

ATC Codes
M01AX21 — Diacerein
Drug Categories
Chemical TaxonomyProvided byClassyfire
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

一般引用
  1. Nicolas P, Tod M, Padoin C, Petitjean O: Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. [Article]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. WHO Diacerein: Restricted Use [Link]
  7. BASG Product Information: Verboril (diacerein) oral capsules [Link]
PubChem Compound
26248
PubChem Substance
347828314
ChemSpider
24456
BindingDB
32018
RxNav
22759
ChEBI
94708
ChEMBL
CHEMBL41286
ZINC
ZINC000003812842
Wikipedia
Diacerein
MSDS
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Clinical Trials

Clinical TrialsLearn More" title="" 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
4 Unknown Status Treatment Osteoarthritis of the Knee 1
3 Completed Treatment Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD/Type 2 Diabetes Mellitus 1
3 Completed Treatment Osteoarthritis in the Hip Joint 1
3 Recruiting Treatment Osteoarthritis of the Knee 1
3 Unknown Status Treatment Osteoarthritis (OA)/Osteoarthritis of the Knee 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Capsule, coated Oral 50 mg
Capsule Oral 50 mg
Capsule Oral
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 Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available

Targets

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Details 1.Oxysterols receptor LXR-alpha
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
分子量
50395.34 Da
References
  1. 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]
Details 2.Oxysterols receptor LXR-beta
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
分子量
50973.375 Da
References
  1. 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
Kind
Group
Organism
Helicobacter pylori
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. 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]
Details 4.Arachidonate 5-lipoxygenase
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
分子量
77982.595 Da
References
  1. 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]
Details 5.Cytochrome P450 1A2
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
分子量
58293.76 Da
References
  1. 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]
Details 6.Cytochrome P450 3A Subfamily (Protein Group)
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
  1. 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]
Details 7.Cytochrome P450 2E1
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
分子量
56848.42 Da
References
  1. 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]
Details 8.Cytochrome P450 2C9
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
分子量
55627.365 Da
References
  1. 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]
Details 9.Cytochrome P450 2D6
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
分子量
55768.94 Da
References
  1. 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