Glucocorticoid receptor (GR)

Hydrocortisone aceponate 0.127% lipophilic cream applied once daily for 3 weeks significantly improved symptoms of steroid-responsive dermatoses (e.g., eczema, psoriasis) in Indian patients. The overall treatment success rate (defined as "excellent" or "good" response based on physician global assessment) was 94.4%, with a mean reduction in disease severity score from baseline to end of treatment (p<0.001). Pruritus, erythema, and scaling showed marked reduction.[1]

Absorption, Distribution and Excretion
Topical corticosteroids are absorbed through normal, intact skin. Skin inflammation and/or other conditions can increase percutaneous absorption. Corticosteroids are primarily metabolized in the liver and then excreted via the kidneys. Some topical corticosteroids and their metabolites are also excreted via bile. Metabolism/Metabolites Primarily metabolized in the liver via CYP3A4. Biological Half-Life 6-8 hours

Hydrocortisone acetate cream showed good safety: no systemic adverse events or hypothalamic-pituitary-adrenal (HPA) axis suppression were observed. Local side effects were mild and uncommon, including transient burning sensation (4.2% of patients) and dry skin (2.8% of patients). No cases of skin atrophy or telangiectasia were reported. [1] Protein binding rate 95%

[1]. A study to evaluate the efficacy and safety of hydrocortisone aceponate 0.127% lipophilic cream in steroid responsive dermatoses in Indian patients. Indian J Dermatol Venereol Leprol. Sep-Oct 2010;76(5):591.

Hydrocortisone acetate is a topical corticosteroid prodrug designed to enhance skin penetration and local activity. In this study, it was used to treat steroid-sensitive skin conditions such as atopic dermatitis and psoriasis. The 0.127% lipophilic cream formulation was chosen because of its higher bioavailability in Indian skin, once daily for up to 3 weeks. Its efficacy and safety support its use as a first-line topical steroid in clinical practice. [1] Hydrocortisone acetate is a corticosteroid hormone. See also: ... See more ...

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Indications For relief of inflammatory and pruritus symptoms in steroid-sensitive skin conditions. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addison's disease). It is also used to treat a variety of immune and allergic diseases such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease. For treatment of inflammatory and pruritus skin conditions in dogs. Used to relieve clinical symptoms associated with canine atopic dermatitis. Used to treat inflammatory and pruritic skin conditions in dogs. Used to relieve clinical symptoms associated with canine atopic dermatitis. Mechanism of Action: Hydrocortisone binds to cytoplasmic glucocorticoid receptors. After binding to the receptor, the newly formed receptor-ligand complex translocates into the cell nucleus, where it binds to multiple glucocorticoid response elements (GREs) in the promoter regions of target genes. The DNA-bound receptor then interacts with basal transcription factors, leading to increased expression of specific target genes. The anti-inflammatory effects of corticosteroids are thought to be related to lipocortin, a phospholipase A2 inhibitory protein that controls the biosynthesis of prostaglandins and leukotrienes by inhibiting arachidonic acid. Specifically, glucocorticoids induce the synthesis of lipocortin-1 (annexin-1), which then binds to the cell membrane, preventing phospholipase A2 from contacting its substrate, arachidonic acid. This results in reduced arachidonic acid production. The expression of cyclooxygenases (COX-1 and COX-2) is also inhibited, thereby enhancing this effect. In other words, the two main products of inflammation—prostaglandins and leukotrienes—are inhibited by glucocorticoids. Glucocorticoids can also stimulate lipocortin-1 to escape into the extracellular space. Lipocortictin-1 binds to leukocyte membrane receptors, inhibiting various inflammatory responses, including epithelial cell adhesion, migration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc.) from neutrophils, macrophages, and mast cells. Furthermore, glucocorticoids suppress the immune system through mechanisms including decreased lymphatic system function, reduced immunoglobulin and complement concentrations, lymphopenia, and interference with antigen-antibody binding.

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Pharmacodynamics
Hydrocortisone is the most important glucocorticoid in the human body. It is essential for life and regulates or supports many important cardiovascular, metabolic, immune, and homeostatic functions.
Topical application of hydrocortisone, due to its anti-inflammatory or immunosuppressive properties, can be used to treat inflammation caused by corticosteroid-induced skin diseases. Glucocorticoids are a class of steroid hormones characterized by their ability to bind to cortisol receptors and trigger a variety of important cardiovascular, metabolic, immune, and homeostatic effects. Glucocorticoids differ from mineralocorticoids and sex steroids in that they have different receptors, target cells, and mechanisms of action. Strictly speaking, the term "corticosteroid" refers to both glucocorticoids and mineralocorticoids, but it is often used synonymously with glucocorticoids. Glucocorticoids suppress cell-mediated immune responses. They act by inhibiting genes encoding cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-α, with IL-2 being the most important. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, leading to a decrease in the amount of IL-2 and its receptor expressed by B cells. This reduces B cell clonal expansion and antibody synthesis. Decreased IL-2 levels also lead to a decrease in the number of activated T lymphocytes.

C26H36O7

460.56

460.246

C, 67.80; H, 7.88; O, 24.32

74050-20-7

72590-77-3 (probutate);57524-89-7 (valerate);508-99-6 (cypionate);125-04-2 (sodium succinate); 2203-97-6 (hemisuccinate anhydrous); 13609-67-1 (butyrate); 50-03-3 (Acetate); 74050-20-7 (aceponate); 50-23-7;

68921

White to off-white solid powder

1.23g/cm3

589.3ºC at 760 mmHg

144-146ºC

192.4ºC

1.552

3.313

1

7

7

33

906

7

CCC(=O)O[C@@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)O)C)C(=O)COC(=O)C

MFBMYAOAMQLLPK-FZNHGJLXSA-N

InChI=1S/C26H36O7/c1-5-22(31)33-26(21(30)14-32-15(2)27)11-9-19-18-7-6-16-12-17(28)8-10-24(16,3)23(18)20(29)13-25(19,26)4/h12,18-20,23,29H,5-11,13-14H2,1-4H3/t18-,19-,20-,23+,24-,25-,26-/m0/s1

[(8S,9S,10R,11S,13S,14S,17R)-17-(2-acetyloxyacetyl)-11-hydroxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] propanoate

Suniderma; Efficort; 74050-20-7; Efficort; Cortavance; Aceponate d'hydrocortisone; Aceponato de hidrocortisona; Hydrocortisoni aceponas; 2340UP1L2G; Hydrocortisone aceponate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~217.13 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)