| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Deflazacort (ML-458; ML458; DL-458-IT, L-5458; Cortax; Decortil; Deflanil; Flezacor; trade name: Emflaza) is a potent glucocorticoid drug approved for use as an anti-inflammatory and immunosuppressant. It was approved by FDA in 2017 to treat patients age 5 years and older with Duchenne muscular dystrophy (DMD). Deflazacort is an inactive prodrug which is metabolized rapidly to the active drug 21-desacetyldeflazacort. Deflazacort results in a significant and equal decrease of thymus weight, indicating a marked reduction in total immunogenic tissue in rats. Deflazacort reduces thymus weight and Daily weight gain in rats. Deflazacort lowers liver IFG-I and GHR mRNA in rats.
| ln Vitro |
The inert prodrug deflazacort quickly transforms into the active metabolite 21-desacetyldeflazacort. After 1.3 hours, maximum 21-desacetyldeflazacort concentrations were measured, with an average of 116 ng/ml. The terminal half-life was 1.3 hours, and the average area under the curve was 280 ng/ml.h. Prednisolone and methylprednisolone were eliminated considerably slower than 21-desacetyldeflazacort[1].
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| ln Vivo |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Deflazacort is rapidly absorbed after oral administration with peak concentration occurring within 1-2 hours. One pharmacokinetic study determined an AUC (area under the curve) of 280 ng/ml · h. The bioavailability of both the oral suspension and tablet are similar. In clinical studies, coadministration of deflazacort crushed with food or applesauce did not affect absorption or bioavailability. Urinary excretion is the major route of deflazacort elimination, accounting for about about 70% of the excreted dose. The remainder of the dose (about 30%) is excreted in the feces. Elimination is almost completed by 24 hours post-dose. 21-deflazacort makes up about 18% of the eliminated drug in the urine. One study determined the volume of distribution to be 204 ± 84 L. 114 ±27 L/h, according to one noncompartmental pharmacokinetic study. The clearance of corticosteroids is enhanced in hypothyroid patients and increased in patients with hyperthyroidism. Dosing adjustments may be considered according to thyroid status. A study of corticosteroid clearance was performed in patients with a creatinine clearance of 15 mL/min or less, and determined that the active metabolite of deflazacort, 21-deflazacort was similar to that in patients with normal renal clearance. Metabolism / Metabolites After oral ingestion, deflazacort is deacetylated at position 21 by plasma esterases, producing the active metabolite 21-deflazacort. 21-deflazacort is then further metabolized by CYP3A4 to inactive metabolite products. Deflazacort 21-OH metabolism is extensive. The metabolite of deflazacort-21-OH is deflazacort 6-beta-OH. Biological Half-Life The half-life of deflazacort ranges from 1.1 to 1.9 h |
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Because no information is available on the use of deflazacort during breastfeeding, an alternate corticosteroid may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants None reported with any corticosteroid. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding The protein binding of the active metabolite of deflazacort is approximately 40%. |
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| References | |||
| Additional Infomation |
Deflazacort is a corticosteroid hormone.
Deflazacort, also known as Emflaza, is a corticosteroid prodrug used as an agent to manage Duchenne Muscular Dystrophy (DMD). It is marketed by Marathon Pharmaceuticals and was approved in February 2017 by the FDA. Duchenne Muscular Dystrophy is an inherited disorder resulting from mutations of the dystrophin gene, which is important for muscle function. This disease can cause serious muscle weakness and progressive breathing and cardiovascular disability, severely impacting patient quality of life and survival. This disease usually manifests by muscle weakness in early childhood followed by loss of the ability to walk (ambulation) as early as age 7. Deflazacort delays the onset of muscle related complications resulting from DMD, prolonging the lives of children diagnosed with this disease and exerting less harmful effects on the bone health and weight than other steroid medications. Deflazacort is a Corticosteroid. The mechanism of action of deflazacort is as a Corticosteroid Hormone Receptor Agonist. Deflazacort is a synthetic glucocorticoid prodrug, with anti-inflammatory and immunomodulating properties. Upon administration, the active metabolite of deflazacort, 21-desacetyl deflazacort, binds to and activates tissue glucocorticoid receptors. This results in the inhibition of specific leukocyte functions and the inhibition of proinflammatory cytokine production. See also: 21-Desacetyldeflazacort (has active moiety). Drug Indication Deflazacort is indicated for the treatment of Duchenne Muscular Dystrophy (DMD) in patients 2 years of age and older. Mechanism of Action Deflazacort is a corticosteroid prodrug with an active metabolite, 21-deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body. The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities. |
| Molecular Formula |
C25H31NO6
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|---|---|
| Molecular Weight |
441.52
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| Exact Mass |
441.215
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| CAS # |
14484-47-0
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| Related CAS # |
Deflazacort-d5;Deflazacort-d7
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| PubChem CID |
189821
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
595.4±50.0 °C at 760 mmHg
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| Melting Point |
255-256.5ºC
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| Flash Point |
313.9±30.1 °C
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| Vapour Pressure |
0.0±3.8 mmHg at 25°C
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| Index of Refraction |
1.661
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| LogP |
2.02
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
996
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| Defined Atom Stereocenter Count |
8
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| SMILES |
CC1=N[C@@]2([C@H](O1)C[C@@H]3[C@@]2(C[C@@H]([C@H]4[C@H]3CCC5=CC(=O)C=C[C@]45C)O)C)C(=O)COC(=O)C
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| InChi Key |
FBHSPRKOSMHSIF-GRMWVWQJSA-N
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| InChi Code |
InChI=1S/C25H31NO6/c1-13-26-25(20(30)12-31-14(2)27)21(32-13)10-18-17-6-5-15-9-16(28)7-8-23(15,3)22(17)19(29)11-24(18,25)4/h7-9,17-19,21-22,29H,5-6,10-12H2,1-4H3/t17-,18-,19-,21+,22+,23-,24-,25+/m0/s1
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| Chemical Name |
[2-[(1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-6,9,13-trimethyl-16-oxo-5-oxa-7-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-6,14,17-trien-8-yl]-2-oxoethyl] acetate
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| Synonyms |
MDL 458; Cortax; Decortil; Deflanil; Flezacor; ML-458; ML458; DL-458-IT, L-5458; trade name: Emflaza
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2649 mL | 11.3245 mL | 22.6490 mL | |
| 5 mM | 0.4530 mL | 2.2649 mL | 4.5298 mL | |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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.
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