Glucocorticoid receptor

In hCMEC/D3 cells, hydrocortisone (50 nM) caused GR transcripts to be downregulated in a dose-dependent manner. The TER of hCMEC/D3 monolayers is significantly increased when hydrocortisone is added to low-serum cell differentiation media [1]. Dendritic cells (DC) treated with hydrocortisone demonstrated decreased expression of MHC II molecules, the costimulatory molecule CD86, and the DC-specific marker CD83. Additionally, there was a significant decrease in the release of IL-12. IFN-γ production was suppressed by hydrocortisone-treated DC, although IL-4 release was enhanced while IL-5 remained unchanged [2]. Perfusion pressure, transudate production, and postischemic oxidative stress are all decreased by hydrocortisone. After ischemia, hydrocortisone prevents the shedding of Syndecan-1, heparan sulfate, and hyaluronic acid while preventing local mast cells from releasing histamine [3].

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

Protein Binding
95%

[1]. Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier. J Physiol. 2008 Apr 1;586(7):1937-49.

[2]. Inhibition of human allergic T-cell responses by IL-10-treated dendritic cells: differences from hydrocortisone-treated dendritic cells. J Allergy Clin Immunol. 2001 Aug;108(2):242-9.

[3]. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007 Nov;107(5):776-84.

Hydrocortisone cyclopentopropionate is a corticosteroid hormone. Drug Indications It is used to relieve inflammatory and itchy symptoms of corticosteroid-sensitive skin diseases. It is also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addison's disease). Additionally, it is used to treat a variety of immune and allergic diseases, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease. Mechanism of Action Hydrocortisone binds to cytoplasmic glucocorticoid receptors. After binding to the receptor, the newly formed receptor-ligand complex translocates to the nucleus and binds to multiple glucocorticoid response elements (GREs) in the promoter regions of target genes. The DNA-bound receptor then interacts with basic transcription factors, leading to increased expression of specific target genes. The anti-inflammatory effect of glucocorticoids is 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 leads to a reduction in the production of arachidonic acid. The expression of cyclooxygenases (COX-1 and COX-2) is also inhibited, thereby enhancing this effect. In other words, two major products of inflammation—prostaglandins and leukotrienes—are inhibited by glucocorticoids. Glucocorticoids 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 a variety of 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 as a synonym for 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 result in a reduction in the number of activated T lymphocytes.

C29H42O6

486.64018

486.298

C, 71.57; H, 8.70; O, 19.73

508-99-6

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;

223253

White to off-white solid powder

1.22g/cm3

645ºC at 760mmHg

208.4ºC

1.572

4.302

2

6

7

35

918

7

C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)COC(=O)CCC5CCCC5)O)C)O

DLVOSEUFIRPIRM-KAQKJVHQSA-N

InChI=1S/C29H42O6/c1-27-13-11-20(30)15-19(27)8-9-21-22-12-14-29(34,28(22,2)16-23(31)26(21)27)24(32)17-35-25(33)10-7-18-5-3-4-6-18/h15,18,21-23,26,31,34H,3-14,16-17H2,1-2H3/t21-,22-,23-,26+,27-,28-,29-/m0/s1

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

HYDROCORTISONE CYPIONATE; 508-99-6; Cortisol 21-cyclopentanepropionate; Hydrocortisone cipionate; NSC-10721; 4XDY25L70B; 17-(3-cyclopentyl-1-propionyl)-11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione; hydrocortisone 21-cyclopentylpropionate;

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 : ~125 mg/mL (~256.86 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.27 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 20.8 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.27 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 20.8 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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