| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg | |||
| 500mg | |||
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| Other Sizes |
| Targets |
glucocorticoid receptor
The primary target of methylprednisolone succinate is the glucocorticoid receptor, a nuclear receptor that regulates gene expression. Upon binding to the glucocorticoid receptor, the compound activates the receptor, which then translocates to the nucleus and modulates the transcription of target genes. This leads to changes in the expression of anti-inflammatory proteins and suppression of pro-inflammatory mediators. Methylprednisolone succinate is a prodrug that is rapidly converted to the active methylprednisolone in vivo, which then exerts its pharmacological effects through the glucocorticoid receptor. |
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| ln Vitro |
IL-10 is an endogenous antiinflammatory cytokine that inhibits TNF biosynthesis and protects mice from lipopolysaccharide (LPS)-induced lethality. As synthetic glucocorticoids are widely used as antiinflammatory agents, we analysed the effects of methylprednisolone administration on IL-10 biosynthesis during murine endotoxaemia. We found that low doses of methylprednisolone (2-10 mg/kg) markedly inhibited TNF production but did not affect serum levels of IL-10, while a high methylprednisolone dose (50 mg/kg) increased LPS-induced IL-10 levels. In parallel, we observed that LPS-induced IL-10 production is TNF-independent in this experimental setting. Experiments conducted in vitro indicated that methylprednisolone (from 0.01 to 100 micrograms/ml) also increased the biosynthesis of IL-10 by LPS-activated mouse peritoneal macrophages. We conclude that methylprednisolone differentially regulates IL-10 and TNF production induced by LPS both in vivo and in vitro at the macrophage level.[1]
In vitro, methylprednisolone succinate exhibits activity in FDA HLAED liver enzyme composite assays, showing both active and marginal composite activities. It also demonstrates bioactivity in a biochemical firefly luciferase enzyme assay for NPC with a potency of 40533.4 nM. As a prodrug, methylprednisolone succinate is rapidly converted to the active methylprednisolone in biological systems. The compound's anti-inflammatory activity is mediated through the glucocorticoid receptor, leading to changes in gene expression and suppression of pro-inflammatory mediators. |
| ln Vivo |
To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.[2]
In vivo, methylprednisolone succinate is a prodrug that is rapidly converted to the active methylprednisolone. It exhibits the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity. Methylprednisolone succinate is used clinically for its potent anti-inflammatory and immunosuppressive properties. The compound is effective in reducing inflammation, suppressing immune responses, and managing a wide range of inflammatory and autoimmune conditions. |
| Enzyme Assay |
For Western blot analysis of B-cell lymphoma-2 (Bcl-2) levels, the primary antibody (sc-7382; Santa Cruz Biotechnology) was diluted 1:200 in 5% skim milk in PBS-T; for protein detection, an HRP-conjugated secondary antibody against mouse IgG was used (Santa Cruz Biotechnology; 1:2000 in 1% skim milk in PBS-T).
p44-p42 MAPK protein levels were detected using a primary antibody (sc-93-G; Santa Cruz Biotechnology) diluted 1:500 in 1% skim milk in PBS-T, and an HRP-conjugated secondary antibody against goat IgG (Santa Cruz Biotechnology; 1:3000 in PBS-T). For Western blot analysis of phospho-p44-phospho-p42 MAPK levels, the primary antibody (Thr180/Tyr182; New England Biolabs) was diluted 1:200 in 1% skim milk in PBS-T; for protein detection, an HRP-conjugated secondary antibody against rabbit IgG was used (Santa Cruz Biotechnology; 1:3000 in PBS-T). Nitric oxide synthase (NOS)1 protein levels were detected using a primary antibody (sc-648; Santa Cruz Biotechnology), diluted 1:200 in 5% skim milk in PBS-T, and an HRP-conjugated secondary antibody against rabbit IgG (Santa Cruz Biotechnology; 1:2000 in 1% skim milk in PBS-T). Cell-free assays for methylprednisolone succinate typically involve assessing its conversion to the active methylprednisolone or its binding to the glucocorticoid receptor. For receptor binding assays, the compound is incubated with recombinant glucocorticoid receptor protein and a radiolabeled ligand (e.g., [3H]-dexamethasone) in a binding buffer. Bound and free ligand are separated by charcoal adsorption or filtration, and the radioactivity is measured. For enzyme activity assays, such as the firefly luciferase assay, the compound is incubated with the enzyme and its substrate, and the luminescence is measured. HPLC methods are used to simultaneously quantify methylprednisolone and methylprednisolone succinate in plasma samples. |
| Cell Assay |
For in vitro cellular experiments, cells expressing the glucocorticoid receptor (e.g., immune cells, fibroblasts) are cultured in appropriate media and treated with methylprednisolone succinate at various concentrations (typically 0.1-100 uM). The compound's ability to activate the glucocorticoid receptor is assessed by measuring the expression of glucocorticoid-responsive genes using qRT-PCR or by using reporter gene assays. Anti-inflammatory effects are assessed by measuring the production of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6) in response to inflammatory stimuli. Cell viability is assessed using MTT or CCK-8 assays to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
Animals were treated with intraperitoneal injections of methylprednisolone (20 mg/kg) or vehicle (0.9% NaCl) on days 1-3 or 4-6 of the disease. Other animal groups received intraperitoneal injections of mifepristone (RU 486) (10 mg/kg) alone, or together with methylprednisolone, or intravitreal injections of cobalt chloride (CoCl2) (2 μl of a 100 mm solution; Sigma) alone, or together with intraperitoneally given methylprednisolone on days 1-3 of the disease. To inhibit the activation of MAPKs, an additional animal group was treated with the intravitreally applied MAPK kinase (MEK) inhibitor 2′-amino-3′-methoxyflavone (PD 98059) (2 μl of a 20 mm solution.[2]
In vivo animal experiments with methylprednisolone succinate typically involve intravenous or intramuscular administration in rodent models of inflammation or autoimmune disease. A common dosing regimen is 1-50 mg/kg body weight, administered as a single dose or daily for 1-4 weeks. For anti-inflammatory studies, animals are treated with the compound before or after induction of inflammation, and inflammatory markers are measured in blood and tissue samples. Pharmacokinetic studies are performed by collecting blood samples at various time points after dosing and measuring plasma drug concentrations by HPLC. The compound is formulated in suitable vehicles such as saline or water. |
| ADME/Pharmacokinetics |
Methylprednisolone succinate is a prodrug with a molecular weight of 474.55 g/mol and a molecular formula of C26H34O8. It is insoluble in water, in contrast to its sodium salt derivative, methylprednisolone sodium succinate, which exhibits water solubility of 100 mg/mL. Following intravenous injection, methylprednisolone sodium succinate is rapidly converted to methylprednisolone with a half-life of 1.7 minutes. Methylprednisolone exhibits linear pharmacokinetics with no dose dependency. It is primarily metabolized in the liver, with some metabolism occurring in the kidneys and tissues. The clearance (CL) of methylprednisolone averages 336 mL/h/kg, the distribution volume (Vd) averages 1.17 L/kg, and the elimination half-life (t1/2) is 2.6 hours.
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| Toxicity/Toxicokinetics |
Methylprednisolone succinate, as a prodrug of methylprednisolone, has a well-characterized safety profile. Methylprednisolone is an intermediate-acting steroid that can stay active for 12 to 36 hours. Common adverse effects associated with glucocorticoid therapy include weight gain, fluid retention, hypertension, hyperglycemia, osteoporosis, and immunosuppression. The risk of adverse effects increases with higher doses and longer duration of therapy. The compound should be used under medical supervision and is intended for clinical use under prescription. For research purposes, it should be handled with standard laboratory precautions.
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| References |
[1] Clin Exp Immunol. 1996 Oct;106(1):91-6.
[2] J Neurosci. 2003 Aug 6;23(18):6993-7000. |
| Additional Infomation |
Methylprednisolone succinate is a corticosteroid and a hemisuccinate. It is a water-soluble ester used to treat emergencies such as cardiac arrest, allergic reactions, and hypoxia.
Methylprednisolone succinate (CAS 2921-57-5) is a synthetic glucocorticoid and a water-soluble prodrug of methylprednisolone. It is extensively used as an anti-inflammatory agent. The compound targets the glucocorticoid receptor, leading to changes in gene expression and suppression of pro-inflammatory mediators. Methylprednisolone succinate exhibits activity in FDA HLAED liver enzyme composite assays and demonstrates bioactivity in biochemical firefly luciferase enzyme assays. Following administration, it is rapidly converted to the active methylprednisolone, which has a plasma half-life of 2.6 hours. Methylprednisolone succinate is used clinically for allergic reactions, autoimmune diseases, and inflammatory disorders. It is also available as a research compound. |
| Molecular Formula |
C26H34O8
|
|---|---|
| Molecular Weight |
474.54336
|
| Exact Mass |
474.225
|
| CAS # |
2921-57-5
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| Related CAS # |
Methylprednisolone;83-43-2;Methylprednisolone succinate sodium;2375-03-3;Methylprednisolone succinate (Standard);2921-57-5
|
| PubChem CID |
16923
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| Appearance |
White to off-white solid
|
| Density |
1.3±0.1 g/cm3
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| Boiling Point |
689.6±55.0 °C at 760 mmHg
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| Flash Point |
230.7±25.0 °C
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| Vapour Pressure |
0.0±4.9 mmHg at 25°C
|
| Index of Refraction |
1.593
|
| LogP |
2.69
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
981
|
| Defined Atom Stereocenter Count |
8
|
| SMILES |
C[C@@]12[C@](C(COC(CCC(O)=O)=O)=O)(O)CC[C@@]1([H])[C@]3([H])C[C@H](C)C4=CC(C=C[C@]4(C)[C@@]3([H])[C@@H](O)C2)=O
|
| InChi Key |
IMBXEJJVJRTNOW-XYMSELFBSA-N
|
| InChi Code |
InChI=1S/C26H34O8/c1-14-10-16-17-7-9-26(33,20(29)13-34-22(32)5-4-21(30)31)25(17,3)12-19(28)23(16)24(2)8-6-15(27)11-18(14)24/h6,8,11,14,16-17,19,23,28,33H,4-5,7,9-10,12-13H2,1-3H3,(H,30,31)/t14-,16-,17-,19-,23+,24-,25-,26-/m0/s1
|
| Chemical Name |
4-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-4-oxobutanoic acid
|
| Synonyms |
Methylprednisolone hydrogen succinate
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ≥ 100 mg/mL (~210.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.27 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 (5.27 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 (5.27 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 | 2.1073 mL | 10.5365 mL | 21.0730 mL | |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2146 mL | |
| 10 mM | 0.2107 mL | 1.0537 mL | 2.1073 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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