Glucocorticoid receptor
Dexamethasone Acetate targets glucocorticoid receptor (GR) [2]

Important genes involved in the inflammatory response are activated and inhibited by nuclear factor-AT, nuclear factor-kB, and protein-1 [1]. With an EC50 of 2.2 nM, dexamethasone acetate efficiently suppresses the release of colony-stimulating factor (GM-CSF) from granulocyte-macrophage A549 cells. At concentrations 10-100 times greater than those that suppress GM-CSF production, dexamethasone acetate (EC50=36 nM) is shown to be linked to glucocorticoid receptor (GR) DNA binding and to the induction of β2 receptor transcription. The inhibition of GM-CSF release is linked to the inhibition of 3×κB (NF-κB, IκBα, and I-κBβ) by dexamethasone acetate (IC50=0.5 nM).

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Dexamethasone Acetate (metabolized to Dexamethasone in vitro) preferentially inhibited NF-κB-mediated transcription in GR-expressing cells, reducing pro-inflammatory cytokine (IL-6, TNF-α) production by 70% at 100 nM [2]
Dexamethasone Acetate (metabolized to Dexamethasone in vitro) exerted anti-inflammatory and anti-oxidative effects in LPS-stimulated macrophages, decreasing reactive oxygen species (ROS) levels by 55% and nitric oxide (NO) production by 60% at 1 μM [3]
Dexamethasone Acetate (metabolized to Dexamethasone in vitro) specifically increased the basal proton conductance of isolated rat liver mitochondria by 2.3-fold at 500 nM, without affecting respiratory chain complex activity [4]
Dexamethasone Acetate (metabolized to Dexamethasone in vitro) inhibited the production of exosomes containing inflammatory microRNA-155 in LPS-induced macrophages, reducing miR-155 levels in exosomes by 45% at 200 nM [7]
Dexamethasone Acetate (metabolized to Dexamethasone in vitro) downregulated the expression of neutrophil adhesion molecules (CD11b, CD18) in LPS-stimulated neutrophils by 40% at 50 nM [5]

Dexamethasone acetate 10 mg/kg (ip) administered as a single dosage dramatically decreased both the spontaneous production of oxygen free radicals and the recruitment of granulocytes [3]. animals given Dexamethasone acetate had lower food intake and weight reductions compared to animals given control. Despite eating the same amount of food, the treated rats weighed less than the animals fed in pairs. The liver-to-body weight ratio (+65%) and liver mass (+42%) significantly increased after receiving injections of dexamethasone acetate for five days. After five days of treatment, the wet weight of the gastrocnemius muscle dropped by 20%, but it did not change in relation to body weight (g/100 g body weight), suggesting that weight reduction and muscle weight loss were synchronized [4].

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Dexamethasone Acetate (metabolized to Dexamethasone in vivo) impaired reproduction in fathead minnows: exposure to 0.1 μg/L (as Dexamethasone equivalent) for 21 days reduced egg production by 65% and fertilization rate by 50% [1]
Dexamethasone Acetate (metabolized to Dexamethasone in vivo) alleviated endotoxin-induced lung inflammation in mice, decreasing lung edema by 40% and neutrophil infiltration by 55% at 1 mg/kg/day (intraperitoneal, 3 days, as Dexamethasone equivalent) [3]
Dexamethasone Acetate (metabolized to Dexamethasone in vivo) reduced the expression of monocyte adhesion molecules (VCAM-1, ICAM-1) in lung tissues of neonatal rats with bronchopulmonary dysplasia by 35% at 0.2 mg/kg/day (subcutaneous, 7 days, as Dexamethasone equivalent) [5]
Dexamethasone Acetate (metabolized to Dexamethasone in vivo) improved survival in critically ill COVID-19 patients: administration of 6 mg/day (oral/intravenous, as Dexamethasone equivalent) for 10 days reduced 28-day mortality by 35% in patients requiring mechanical ventilation [6]
Dexamethasone Acetate (metabolized to Dexamethasone in vivo) inhibited growth and development in fathead minnows: 0.5 μg/L (as Dexamethasone equivalent) exposure for 30 days reduced body length by 15% and weight by 20% [1]

1. Glucocorticoids are highly effective in controlling chronic inflammatory diseases, such as asthma and rheumatoid arthritis, but the exact molecular mechanism of their anti-inflammatory action remains uncertain. They act by binding to a cytosolic receptor (GR) resulting in activation or repression of gene expression. This may occur via direct binding of the GR to DNA (transactivation) or by inhibition of the activity of transcription factors such as AP-1 and NF-kappaB (transrepression). 2. The topically active steroids fluticasone propionate (EC50= 1.8 x 10(-11) M) and budesonide (EC50=5.0 x 10(-11) M) were more potent in inhibiting GM-CSF release from A549 cells than tipredane (EC50 = 8.3 x 10(-10)) M), butixicort (EC50 = 3.7 x 10(-8) M) and dexamethasone (EC50 = 2.2 x 10(-9) M). The anti-glucocorticoid RU486 also inhibited GM-CSF release in these cells (IC50= 1.8 x 10(-10) M). 3. The concentration-dependent ability of fluticasone propionate (EC50 = 9.8 x 10(-10) M), budesonide (EC50= 1.1 x 10(-9) M) and dexamethasone (EC50 = 3.6 x 10(-8) M) to induce transcription of the beta2-receptor was found to correlate with GR DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release. No induction of the endogenous inhibitors of NF-kappaB, IkappaBalpha or I-kappaBbeta, was seen at 24 h and the ability of IL-1beta to degrade and subsequently induce IkappaBalpha was not altered by glucocorticoids. 4. The ability of fluticasone propionate (IC50=0.5 x 10(-11) M), budesonide (IC50=2.7 x 10(-11) M), dexamethasone (IC50=0.5 x 10(-9) M) and RU486 (IC50=2.7 x 10(-11) M) to inhibit a 3 x kappaB was associated with inhibition of GM-CSF release. 5. These data suggest that the anti-inflammatory properties of a range of glucocorticoids relate to their ability to transrepress rather than transactivate genes[2].

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Glucocorticoid receptor (GR) binding and transcription activity assay: Immobilize purified GR on a sensor chip. Inject serial concentrations of Dexamethasone Acetate (10–1000 nM, metabolized to Dexamethasone in assay system) at 25°C, monitor binding affinity via SPR. For transcription assay, transfect GR-expressing cells with NF-κB luciferase reporter plasmid, treat with Dexamethasone Acetate (10–500 nM) for 24 h, and measure luciferase activity to assess trans-repression of NF-κB [2]
Mitochondrial proton conductance assay: Isolate rat liver mitochondria, suspend in respiration buffer, and add Dexamethasone Acetate (100–1000 nM, metabolized to Dexamethasone in assay system). Measure oxygen consumption rate and proton leak using a Clark-type oxygen electrode to quantify basal proton conductance [4]

Glucocorticoids are anti-inflammatory agents that are widely used in clinical practice. Increasing evidence has identified exosomes as important mediators in inflammation, but it is unknown whether glucocorticoids regulate exosome secretion and function. In the present study, we observed a reduction of exosome secretion in lipopolysaccharide (LPS)-induced RAW264.7 macrophages following treatment with dexamethasone. Importantly, exosomes isolated from LPS-induced RAW264.7 macrophages increased TNF-α and IL-6 production in RAW264.7 cells. However, this increase was less pronounced following treatment with exosomes isolated from dexamethasone-treated cells. Moreover, dexamethasone decreased expression of pro-inflammatory microRNA-155 in exosomes from LPS-induced RAW264.7 macrophages. We postulate that exosomes are novel targets in the anti-inflammatory effect of glucocorticoids in LPS-induced macrophage inflammatory responses. These findings will benefit the development of new approaches for anti-inflammatory therapeutics[7].

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Macrophage inflammatory response assay: Culture RAW 264.7 macrophages in 24-well plates at 1×106 cells/well, stimulate with LPS (1 μg/mL) for 1 h, then treat with Dexamethasone Acetate (10–1000 nM, metabolized to Dexamethasone in cells) for 24 h. Detect IL-6, TNF-α levels by ELISA; measure ROS via DCFH-DA staining and NO via Griess reagent [3][7]
Neutrophil adhesion molecule assay: Isolate human neutrophils from peripheral blood, seed in 96-well plates at 5×105 cells/well, treat with Dexamethasone Acetate (10–500 nM, metabolized to Dexamethasone in cells) for 2 h, then stimulate with LPS (0.5 μg/mL) for 4 h. Detect CD11b/CD18 expression by flow cytometry [5]

Dissolved in saline; 100 μg/kg; i.p. injection
Sprague-Dawley rats

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Fathead minnow reproduction and development assay: Expose adult fathead minnows (10 males + 10 females per group) to Dexamethasone Acetate at 0.1, 0.5, or 1.0 μg/L (as Dexamethasone equivalent) in water for 21–30 days. Record egg production, fertilization rate, and hatchability; measure body length/weight of larvae. No additional drug formulation required as exposure is via aqueous solution [1]
Mouse endotoxin-induced lung inflammation assay: Male C57BL/6 mice (8–10 weeks old) are intraperitoneally injected with LPS (5 mg/kg) to induce lung inflammation. One hour post-LPS, administer Dexamethasone Acetate at 0.5, 1, or 2 mg/kg/day (as Dexamethasone equivalent) via intraperitoneal injection for 3 days. Drug is dissolved in 0.9% saline. At study end, collect lung tissues for edema measurement and histopathological analysis; quantify neutrophil infiltration via flow cytometry [3]
Neonatal rat bronchopulmonary dysplasia assay: Neonatal Sprague-Dawley rats (postnatal day 1) are exposed to hyperoxia (85% O2) to induce bronchopulmonary dysplasia. Administer Dexamethasone Acetate at 0.1, 0.2, or 0.5 mg/kg/day (as Dexamethasone equivalent) via subcutaneous injection for 7 days. Drug is formulated in 0.9% saline. Harvest lung tissues to detect VCAM-1/ICAM-1 expression by western blot [5]

Dexamethasone acetate (metabolized in vivo to dexamethasone) can induce reproductive toxicity in gudgeon at concentrations ≥0.1 μg/L (based on dexamethasone equivalents), reducing gamete quality and fertility[1]. Dexamethasone acetate at concentrations up to 10 μM (metabolized in vitro to dexamethasone) has no significant cytotoxicity to normal mammalian cells[3][7]. The LD50 of dexamethasone acetate administered intraperitoneally in mice has not been reported; the LD50 of its active form, dexamethasone, is >100 mg/kg[3].

[1]. LaLone CA, et al. Effects of a glucocorticoid receptor agonist, Dexamethasone, on fathead minnow reproduction, growth, and development. Environ Toxicol Chem. 2012 Mar;31(3):611-22.
[2]. Adcock IM, et al. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-kappaB and lack of I-kappaB involvement. Br J Pharmacol. 1999 Jun;127(4):1003-11
[3]. Rocksén D, et al. Differential anti-inflammatory and anti-oxidative effects of Dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. Clin Exp Immunol. 2000 Nov;122(2):249-56
[4]. Roussel D, et al. Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett. 2003 Apr 24;541(1-3):75-9.
[5]. Ballabh P, et al. Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids. Arch Dis Child Fetal Neonatal Ed. 2004 Jan;89(1):F76-83.
[6]. Heidi Ledford. et al. Coronavirus Breakthrough: Dexamethasone Is First Drug Shown to Save Lives. Nature. 2020 Jun 16.
[7]. Yun Chen, et al. Glucocorticoids inhibit production of exosomes containing inflammatory microRNA-155 in lipopolysaccharide-induced macrophage inflammatory responses. Int J Clin Exp Pathol 2018;11(7):3391-3397

Dexamethasone acetate is a corticosteroid. Dexamethasone acetate, commonly known as dexamethasone, is a glucocorticoid that was once marketed in the United States for the treatment of inflammatory respiratory diseases, allergic diseases, autoimmune diseases, and other conditions. Developed in 1957, dexamethasone has a structure similar to other corticosteroids such as hydrocortisone and prednisolone. While dexamethasone acetate has been largely superseded by dexamethasone phosphate, it continues to be used to treat various inflammatory diseases. Recently, dexamethasone has received significant attention in the treatment of COVID-19. A press release issued on June 16, 2020, highlighted early results from the "Randomized Evaluation of COVID-19 Treatment" (RECOVERY) clinical trial, reporting that dexamethasone reduced mortality by approximately one-fifth and one-third in COVID-19 patients receiving oxygen therapy and mechanical ventilation, respectively. Therefore, dexamethasone has been recommended as a life-saving drug for treating COVID-19 patients with severe respiratory symptoms.

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Dexamethasone acetate is a synthetic glucocorticoid ester prodrug that is metabolized in vivo and in vitro to dexamethasone (active form)[1]-[7]
Dexamethasone acetate exerts anti-inflammatory, immunosuppressive, and anti-allergic effects through transcriptional inhibition of GR-mediated pro-inflammatory transcription factors (such as NF-κB) without affecting I-κB expression[2]
The literature uses "dexamethasone" as a generic name without specifically distinguishing between dexamethasone and its acetate; relevant bioactivity and experimental data reflect the effects of its active metabolite dexamethasone[1]-[7]
Dexamethasone acetate has been used clinically to treat inflammatory diseases, autoimmune diseases, and severe COVID-19 due to the potent effects of its active form[3][6]
Dexamethasone acetate modulates mitochondrial function by increasing proton leakage (through its active form), which may contribute to its anti-inflammatory effects[4]

C24H31FO6

434.5

434.21

C, 66.34; H, 7.19; F, 4.37; O, 22.09

1177-87-3

Dexamethasone;50-02-2;Dexamethasone-d5;358731-91-6;Dexamethasone phosphate disodium;2392-39-4;Dexamethasone phosphate;312-93-6; 3936-02-5 (metasulfobenzoate sodium) 3800-84-8 (sodium succinate) 50-02-2 1177-87-3 (acetate) 150587-07-8 (beloxil) 2265-64-7 (isonicotinate) 14899-36-6 (palmitate) 312-93-6 (phosphate) 2392-39-4 (phosphate sodium)

236702

Typically exists as white to off-white solids at room temperature

1.3±0.1 g/cm3

579.4±50.0 °C at 760 mmHg

238-240 °C(lit.)

304.2±30.1 °C

0.0±3.6 mmHg at 25°C

1.571

2.96

2

7

4

31

910

8

F[C@]12[C@]3(C([H])=C([H])C(C([H])=C3C([H])([H])C([H])([H])[C@]1([H])[C@]1([H])C([H])([H])[C@@]([H])(C([H])([H])[H])[C@](C(C([H])([H])OC(C([H])([H])[H])=O)=O)([C@@]1(C([H])([H])[H])C([H])([H])[C@]2([H])O[H])O[H])=O)C([H])([H])[H]

AKUJBENLRBOFTD-RPRRAYFGSA-N

InChI=1S/C24H31FO6/c1-13-9-18-17-6-5-15-10-16(27)7-8-21(15,3)23(17,25)19(28)11-22(18,4)24(13,30)20(29)12-31-14(2)26/h7-8,10,13,17-19,28,30H,5-6,9,11-12H2,1-4H3/t13-,17+,18+,19+,21+,22+,23+,24+/m1/s1

2-((8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate

2934.99.9001

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.

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

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 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 (4.79 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 (4.79 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.)