21-desacetyl Deflazacort
(Synonyms: L-6,485) 目录号 : GC42087
A glucocorticoid
Cas No.:13649-57-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
21-desacetyl Deflazacort is the active glucocorticoid derived from the prodrug deflazacort . 21-desacetyl Deflazacort and related glucocorticoids have anti-inflammatory and immunosuppressant effects, as well as benefits in certain muscular dystrophies.
| Cas No. | 13649-57-5 | SDF | |
| 别名 | L-6,485 | ||
| Canonical SMILES | O=C1C=C[C@@]2(C)C(CC[C@]3([H])[C@]2([H])[C@@H](O)C[C@@]4(C)[C@@]3([H])C[C@]5([H])[C@@]4(C(CO)=O)N=C(C)O5)=C1 | ||
| 分子式 | C23H29NO5 | 分子量 | 399.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5031 mL | 12.5156 mL | 25.0313 mL |
| 5 mM | 0.5006 mL | 2.5031 mL | 5.0063 mL |
| 10 mM | 0.2503 mL | 1.2516 mL | 2.5031 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Metabolite V, an epoxide species is a minor circulating metabolite in humans following a single oral dose of deflazacort
Pharmacol Res Perspect 2020 Dec;8(6):e00677.PMID:33090712DOI:10.1002/prp2.677.
Deflazacort (Emflaza) was approved in the United States in 2017 for the treatment of the Duchenne muscular dystrophy in patients aged 2 years and older. Several deflazacort metabolites were isolated and identified from rats, dogs, monkeys, and humans. Among them, 1ß,2ß-epoxy-3ß-hydroxy-21-desacetyl deflazacort, referred to as Metabolite V, was reported to be one of the major circulating metabolites in humans. However, its quantitative distribution in plasma was not fully characterized. The objective of this study was to determine deflazacort plasma pharmacokinetics, metabolite profiles and their quantitative exposures in humans following a single oral dose. Six healthy male subjects were each administered a single oral dose of 60 mg [14 C]-deflazacort. Plasma and urine were collected and deflazacort metabolites in plasma were quantified by high performance liquid chromatography radio-profiling followed by liquid chromatography-mass spectrometry characterization. Metabolite V was isolated from urine and its structure was further confirmed by nuclear magnetic resonance analysis. These analyses demonstrated that deflazacort was not detectable in plasma; of the eight circulating deflazacort metabolites identified or characterized, the pharmacologically active metabolite 21-desacetyl Deflazacort and inactive metabolite 6ß-hydroxy-21-desacetyl deflazacort accounted for 25.0% and 32.9% of the 0-24 hours plasma total radioactivity, respectively, while Metabolite V, an epoxide species, was a minor circulating metabolite, representing only about 4.7% of the total plasma radioactivity.
Disposition and metabolism of a new steroidal anti-inflammatory agent, deflazacort, in cynomolgus monkeys
Xenobiotica 1983 Mar;13(3):185-96.PMID:6613164DOI:10.3109/00498258309052253.
The kinetics and metabolic fate of 2'-14C-deflazacort, a new steroidal antiinflammatory agent, were studied in the cynomolgus monkey after both p.o. and i.v. administration (5 mg/kg). There is no unchanged deflazacort in the plasma or urine after either p.o. or i.v. treatment. As judged from the plasma AUC and urinary elimination values, the oral availability of both total 14C and metabolites seems to be lowered because of a route-dependent first-pass. Both radioactivity and the main metabolite (21-desacetyl Deflazacort) are eliminated from the plasma with half-lives of 2--3-5 h. The i.v. administered 14C is eliminated mainly in the urine (52--55% of dose), but biliary excretion is also quantitatively important. Six metabolites were isolated from urine and identified by physico-chemical analysis. Among them desacetylated deflazacort and its 6 beta-hydroxy derivative were shown to be the major radioactive products in plasma and urine, respectively. Minor metabolites were: 21-desacetyl, 6 alpha-hydroxy deflazacort; 21-desacetyl, 5 alpha, 1-eno, deflazacort; 21-desacetyl, 20 beta hydroxy deflazacort; and 21-desacetyl, 11-keto deflazacort.
The effect of food on the relative bioavailability of deflazacort
Eur J Drug Metab Pharmacokinet 1996 Jul-Sep;21(3):241-5.PMID:8980922DOI:10.1007/BF03189720.
The effect of high- and low-fat meals on the relative bioavailability of deflazacort tablets was investigated in 12 healthy, adult males who were administered 36 mg deflazacort under fasted and fed conditions in a crossover fashion. Serial plasma samples were drawn up to 24 h post-dose and quantified for the active metabolite 21-desacetyl Deflazacort (DFZ 21-OH) by a rapid and sensitive HPLC method. Following deflazacort administration with high-fat and low-fat meals and under fasted conditions, DFZ 21-OH area under the curve to infinity averaged 508.39 +/- 131.70, 510.05 +/- 148.30 and 511.90 +/- 188.16 ng.h/ml. DFZ 21-OH Cmax averaged 156.31 +/- 33.31, 156.85 +/- 40.17 and 188.05 +/- 53.35 ng/ml for high-fat, low-fat and fasted treatments, respectively. Differences in Cmax between the fed versus fasted treatments were statistically significant (P < 0.05). The decrease in Cmax under fed conditions was accompanied by an increase in mean Tmax of approximately 17-85% compared to fasted conditions. As expected, terminal half-life was not affected. These data indicate that co-administration of deflazacort tablets with high-fat and low-fat meals leads to a small decrease in rate but does not affect its extent of absorption.
An investigation of the dose proportionality of deflazacort pharmacokinetics
Biopharm Drug Dispos 1996 Dec;17(9):753-60.PMID:8968528DOI:10.1002/(SICI)1099-081X(199612)17:9<753::AID-BDD988>3.0.CO;2-D.
The dose proportionality of deflazacort was assessed following single-dose oral administration at doses of 3, 6, and 36 mg to 24 healthy young adult volunteers. The active metabolite of deflazacort (21-desacetyl Deflazacort) was monitored in plasma using a sensitive, semi-microbore liquid chromatographic method. Cmax averaged 10.4 +/- 5.0, 19.8 +/- 7.5, and 132.6 +/- 52.5 ng mL-1 for the 3, 6, and 36 mg doses, respectively. AUC(0-infinity) averaged 38.5 +/- 37.1, 64.9 +/- 20.8, and 411.7 +/- 148.5 ng h mL-1 for the same three doses, respectively. Elimination half-life ranged from 1.9 +/- 0.5 h at the 6 mg dose to 2.4 +/- 1.5 h at the 36 mg dose. Regression analyses of dose versus Cmax and AUC(0-infinity) yielded intercepts which were not significantly different from zero (p > 0.05) and slopes which were significant (p < 0.05). Regression analysis of dose versus apparent oral clearance yielded a slope which was not significantly different from zero (p > 0.05). These data indicate that deflazacort exhibits dose-proportional pharmacokinetics.
Differential binding in vitro to glucocorticoid receptors of deflazacort and prednisolone
Eur J Pharmacol 1981 Dec 17;76(4):427-30.PMID:7327211DOI:10.1016/0014-2999(81)90115-1.
Deflazacort, a new steroidal anti-inflammatory agent, has remarkable glucocorticoid activity in both animals and humans. Its biologically active form, 21-desacetyl Deflazacort, displaces [3H]dexamethasone from its cytosol receptor sites in rat kidney, thymus and liver in vitro. Although less active than prednisolone in its binding to glucocorticoid receptors, deflazacort 'stabilizes' the resulting steroid-receptor complex more effectively than the former in the kidney and thymus but not in the liver. This property might explain the greater activity of deflazacort than of prednisolone in the rat.