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Diacerein ( Diacerhein; Diacetylrhein) is slow-acting medication which acts as a potent inhibitor of pro-inflammatory cytokine Interleukin-1B (IL-1B) production, it is indicated for osteoarthritis and chronic inflammatory arthritis. Diacerein significantly inhibits LPS-induced IL-1beta production by synovial tissue and cartilage. Diacerein (1 μM) has a significantly less inhibitory effect on cartilage synthesis than culture media containing LPS only.
Physicochemical Properties
| Molecular Formula | C19H12O8 | |
| Molecular Weight | 368.29 | |
| Exact Mass | 368.053 | |
| CAS # | 13739-02-1 | |
| Related CAS # | Diacerein-d6;1325559-27-0 | |
| PubChem CID | 26248 | |
| Appearance | Light yellow to yellow solid powder | |
| Density | 1.5±0.1 g/cm3 | |
| Boiling Point | 631.5±55.0 °C at 760 mmHg | |
| Melting Point | 217-2180C | |
| Flash Point | 231.8±25.0 °C | |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C | |
| Index of Refraction | 1.634 | |
| LogP | 1.99 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 27 | |
| Complexity | 683 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | TYNLGDBUJLVSMA-UHFFFAOYSA-N | |
| InChi Code | 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) | |
| Chemical Name | 4,5-diacetyloxy-9,10-dioxoanthracene-2-carboxylic acid | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Bioavailability of 50-60%. Entirely converted to the active metabolite rhein [DB13174] before reaching systemic circulation. 37% excreted in urine and 53% in feces as estimated in rats. 15-60L. Total CL is 1.5L/h and renal CL is 0.1L/h. Metabolism / Metabolites Entirely converted to rhien [DB13174] through double deacetylation before reaching systemic circulation. Rhein [DB13174] is further metabolized to rhein glucuronide and rhein sulfate. Biological Half-Life 4-10h. |
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| Toxicity/Toxicokinetics |
Protein Binding 99% of rhein is bound to plasma proteins. |
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| References | Osteoarthritis Cartilage.1999 May;7(3):272-80;Osteoarthritis Cartilage.1999 May;7(3):255-64. | ||
| Additional Infomation |
4,5-diacetyloxy-9,10-dioxo-2-anthracenecarboxylic acid is an anthraquinone. 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. Diacerein is under investigation for the treatment of Insulin Resistance, Diabetes Mellitus (Type 2), and Diabetes-Related Complications. Drug Indication For the treatment of osteoarthritis affecting the hip or knee. Mechanism of Action Diacerein's active metabolite rhein [DB13174] 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. 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. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism. Pharmacodynamics Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (13.58 mM) in 1% (w/v) carboxymethylcellulose (CMC) (add these co-solvents sequentially from left to right, and one by one), suspension solution. Solubility in Formulation 2: 1%CMC Na : 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7153 mL | 13.5763 mL | 27.1525 mL | |
| 5 mM | 0.5431 mL | 2.7153 mL | 5.4305 mL | |
| 10 mM | 0.2715 mL | 1.3576 mL | 2.7153 mL |