| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
|
||
| 1g | |||
| Other Sizes |
Purity: ≥98%
| ln Vitro |
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. Diacerein (1 μM) decreases NO release in synovial tissue and cartilage media and increases IL-1ra levels in cartilage culture media. Diacerein (10 μM) enhances the expression of TGF-beta1 and TGF-beta2 in cultured bovine articular chondrocytes. Diacerein reduces, in a dose-dependent manner, the interleukin-1-beta (IL-1beta)-induced MMP-13 production in osteoarthritic subchondral bone. Diacerein significantly reduces the activity of MMP-13 and cathepsin K in osteoclasts. Diacerein effectively blocks the IL-1beta effect on the osteoclast differentiation process and the survival of mature osteoclasts.
In human OA synovial tissue cultures stimulated with LPS (1 μg/ml), Diacerein at 10⁻⁶ M significantly inhibited IL-1β secretion (P<0.05 vs LPS). [1] In human OA cartilage cultures stimulated with LPS, Diacerein at 10⁻⁶ M and 10⁻⁵ M induced a dose-dependent decrease of IL-1β production (P<0.05 vs LPS at both concentrations). [1] Diacerein at 10⁻⁶ M reversed the inhibitory effect of LPS on cartilage ³⁵S-GAG synthesis (proteoglycan synthesis), being 89±24% as effective as rhein at equivalent concentrations. [1] Conditioned media from synovial tissue cultured with LPS plus Diacerein (10⁻⁶ M) significantly reversed the inhibitory effect of LPS-conditioned media on ³⁵S uptake by human cartilage cultures (P<0.02 vs LPS). [1] Diacerein at 10⁻⁵ M decreased LPS-stimulated NO release in human synovial tissue cultures (P<0.002 vs LPS) and in human cartilage cultures (P<0.001 vs LPS). [1] Diacerein at 10⁻⁵ M significantly inhibited LPS-induced IL-1ra production in synovial tissue cultures (P<0.001 vs LPS). [1] Diacerein at 10⁻⁶ M and 10⁻⁵ M significantly stimulated IL-1ra secretion in human cartilage cultures (P<0.05 and P<0.002 respectively vs LPS). [1] Diacerein at 10⁻⁵ M and 10⁻⁶ M did not show any deleterious effect on synovial fibroblast viability (>90% compared to controls). [1] |
|---|---|
| ln Vivo |
Diacerein (100 mg/kg/day) significantly suppresses the paw edema and the increase in serum mucoprotein in the adjuvant-induced arthritic rats. Diacerein (30 mg/kg/day) combined with Naproxen (3 mg/kg/day) results in significantly greater anti-inflammatory activity than with naproxen alone in the adjuvant-induced arthritic rats. Diacerein (100 mg/kg/day) also significantly prevents bone loss and reduces the serum alkaline phosphatase and decreases the excretion of urinary hydroxyproline in the ovariectomized rats. Diacerein (25 mg/kg) decreases the thickness of cartilage and subchondral bone in the lesion (middle) zone of the lateral tibial plateau in Merino wethers.
|
| Cell Assay |
Synovial tissue organ culture: Human OA synovial tissue was cut into small pieces (few mm diameter, approx. 80 mg per sample) and cultured in 2 ml RPMI 1640 supplemented with L-glutamine (2 mM), penicillin (100 U/ml) and streptomycin sulphate (100 μg/ml). Test materials including Diacerein (10⁻⁷ to 10⁻⁵ M) were added, and after 48 h incubation (37°C, 5% CO₂), supernates were collected for IL-1β, NO, and IL-1ra assays. [1]
Cartilage culture: Human OA cartilage was finely diced, randomized, and distributed in 96-well plates (approx. 15 mg cartilage per well) in 0.2 ml DMEM with 1% FCS, penicillin, and streptomycin. Test materials including Diacerein (10⁻⁷ to 10⁻⁵ M) were added. After 24 h, ³⁵SO₄ (final 40 μCi/ml) was added, and after two more days of incubation, supernates and cartilage were collected for ³⁵S-GAG determination. Separate cultures without radioactive material were used for IL-1β, IL-1ra, and NO assays after 48 h incubation. [1] Cell viability assay: Human synovial fibroblast monolayer cultures were exposed to Diacerein (10⁻⁵ to 10⁻⁷ M) for 72 h, and viability was determined by trypan blue exclusion test. Toxicity was also evaluated by tritiated thymidine incorporation into DNA. [1] |
| Animal Protocol |
30, 100 mg/kg Rats
|
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Bioavailability is 50-60%. It is completely converted to the active metabolite emodin [DB13174] before entering systemic circulation. Estimated in rats, 37% is excreted in the urine and 53% in the feces. Volume: 15-60 L. Total clearance: 1.5 L/h; renal clearance: 0.1 L/h. Metabolism/Metabolite Before entering systemic circulation, it is completely converted to emodin [DB13174] via double deacetylation. Emodin [DB13174] is further metabolized to emodin glucuronide and emodin sulfate. Biological Half-Life 4-10 hours. In humans, the maximum plasma concentration of Diacerein was 11 μM after a single oral dose of 50 mg. [1] Following daily administration of 50 mg Diacerein every 12 h for one month, its active metabolite rhein was found in synovial fluid at concentrations in the 1–10 μM plasma range. [1] |
| Toxicity/Toxicokinetics |
Protein Binding
99% of emodin binds to plasma proteins. Diacerein at concentrations of 10⁻⁵ to 10⁻⁷ M added to synovial fibroblast monolayer cultures for 72 h showed no deleterious effect on cell viability, which remained >90% compared to controls. [1] Diacerein used at concentrations up to 10⁻⁵ M was devoid of cell toxicity. [1] |
| References |
Osteoarthritis Cartilage.1999 May;7(3):272-80;Osteoarthritis Cartilage.1999 May;7(3):255-64.
|
| Additional Infomation |
4,5-Diaacetoxy-9,10-dioxo-2-anthracarboxylic acid is an anthraquinone compound. Diacerein is a prodrug that is metabolized to emodin. Currently, diacerein is approved in France for the treatment of osteoarthritis, but its use is limited due to its side effects, including severe diarrhea. Diacerein is being investigated for the treatment of insulin resistance, type 2 diabetes, and its complications. Drug Indications For the treatment of osteoarthritis of the hip or knee. Mechanism of Action The active metabolite of diacerein, emodin [DB13174], reduces cartilage destruction by decreasing the expression of matrix metalloproteinases (MMPs)-1 and -3, and by upregulating the expression of tissue inhibitors of matrix metalloproteinases (TIMPs), which can reduce the activity of multiple MMPs. The anti-inflammatory effects of emodin can reduce the activity level of interleukin-1β, which plays an important role in reducing extracellular matrix production, MMP activity, and persistent inflammation. Emodin reduces the synthetic activity of abnormal osteoblasts through an unknown mechanism.
Pharmacodynamics Reduces inflammation and cartilage destruction, and corrects abnormal osteoblast activity. Diacerein (ART 50) is marketed in France by Negma for the treatment of osteoarthritis. It is currently under evaluation as a disease-modifying OA drug (DMOAD) in a 3-year, randomized, double-blind, placebo-controlled clinical study of 500 patients with OA of the hip (ECHODIAH study). [1] Diacerein showed anti-OA effects in experimental animal OA models (references cited but not part of this study's own data). [1] The mechanism of action of Diacerein involves antagonism of IL-1 effects on cartilage matrix components and collagenolytic activity, with no effect on phospholipase A2, cyclo-oxygenase, and 5-lipoxygenase. [1] |
| 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
|
|
| Synonyms |
|
|
| 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 |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA