Glucocorticoid Receptor/GR

糠酸莫米松附着在糖皮质激素受体上，引起受体构象变化，与伴侣分离，受体进入细胞核[1]。糠酸莫米松（0.1-10 μM；LPS 刺激前 2 小时）以浓度依赖性方式显着抑制 J774 巨噬细胞中 LPS 刺激的亚硝酸盐生成，J774 细胞中糠酸莫米松的 IC50 值为 0.00024 μM[1]。糠酸莫米松（0.1-10 μM；LPS 刺激前 2 小时）比 DEX 更强大，它在 0.01 μM 剂量下显着降低 iNOS 表达，而 Dex 在 0.1 μM 剂量下变得活跃。此外，0.01 µM 的 cox-2 蛋白表达抑制率对于糠酸莫米松为 79%，对于 Dex 为 39%[1]。

莫米松会减少大鼠揉鼻的次数，并且在治疗期间观察到这种反应受到抑制。在小鼠中测试的最高剂量下，莫米松 (3 mg/kg) 可抑制气道对雾化醋甲胆碱敏感性的增加。最后一次过敏原激发后一小时给予莫米松，剂量依赖性地抑制过敏原诱导的 Penh 增加，与激发前的治疗方案相比，效力损失约 10 倍。糠酸莫米松（0.02%）和丙酸氟替卡松（0.1%）即使在局部应用后6小时也能显着抑制抗原诱导的鼻摩擦增加，表明这两种药物具有长效作用。糠酸莫米松剂量依赖性地抑制致敏、卵清蛋白攻击小鼠的支气管肺泡灌洗液和肺组织中嗜酸性粒细胞数量的升高。糠酸莫米松 (33 mg/kg) 可将 CD44+ T 辅助细胞（活化/记忆细胞）的百分比降低至在未致敏、卵清蛋白攻击的小鼠中观察到的水平。

细胞外信号调节激酶1/2（pERK1/2）、PARP-1和Bax的表达[1]
根据脊髓组织的标准化方案，通过SDS页面电泳和印迹评估脊髓中特异性抗体的蛋白质含量。 在4°C下用兔磷酸化p44/42 MAPK（pERK1/2）、兔PARP-1、兔Bax对膜进行过夜探测。在室温下与辣根过氧化物酶偶联的抗兔孵育1小时后，使用增强化学发光系统产生信号。p44/42 MAPK（ERK1/2）用于规范磷酸化p44/42 MAPK的信号，而β-actin和GAPDH分别用于规范PARP-1和Bax的表达。

小鼠单核细胞/巨噬细胞J774细胞系在添加了2 mM谷氨酰胺、25 mM Hepes、青霉素（100 U/ml）、链霉素（100μg/ml）、10%胎牛血清（FBS）和1.2%丙酮酸钠的Dulbecco改良Eagles培养基（DMEM）中生长。将细胞以2.5±105个细胞/ml的密度接种在24孔培养板上，或接种在直径60 mm的培养皿中（每3 ml培养皿3±106个细胞），并在37°C的5%CO2中粘附。24小时后，用浓度逐渐增加的旧（Dex和MET）和新的糠酸莫米松（MF）预处理细胞（2小时），并用来自大肠杆菌的LPS（血清型0111:B4，10μg/ml）刺激。处理24小时后，收集上清液进行亚硝酸盐测定[1]。

Mice were randomly allocated into the following groups (n = 60 total animals): [1]
Sham group (n = 5): Mice not subjected to SCI but only to T5–T8 vertebrae exposition, sacrificed as control.[1]
SCI group (n = 10): Mice were subjected to surgical operations to induce SCI and injected with saline;[1]
SCI + mometasone furoate (MF)  (n = 10): Mice were subjected to surgical operations to induce SCI and treated with mometasone furoate (MF)  0.1 mg/Kg;[1]
SCI + Dex (n = 10): Mice were subjected to surgical operations to induce SCI and treated with Dex 1 mg/Kg;[1]
SCI + MPSS (n = 10): Mice were subjected to surgical operations to induce SCI and treated with MPSS 6 mg/Kg.[1]
In another experimental set, investigated drugs were preliminary tested in order to evaluate a more efficient dosage. Moreover, control groups (not included in the present work) designed as “Sham + mometasone furoate (MF)  ” (n = 5), “Sham + Dex” (n = 5), “Sham + MPSS” (n = 5), “Sham + vehicle (5% DMSO)” (n = 5) were tested to evaluate toxicity of GC as well as vehicle (DMSO) injection.[1]
Mice were treated i.p. 30 min following trauma induction and once a day for 7 days until sacrifice.[1]
Spinal cord area, corresponding to the thoracic spine, was sampled, in order to evaluate the various parameters.[1]

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3 mg/kg

ovalbumin-challenged mice

Absorption, Distribution and Excretion
The average time to peak concentration is 1.0 to 2.5 hours. Bioavailability has been reported to be less than 1%, but studies with repeated administration of inhaled corticosteroids have shown a bioavailability of 11%. The bioavailability of the 0.1% ointment may be 0.7%. Approximately 74% of the inhaled dose is excreted in feces, and 8% in urine. The steady-state volume of distribution is 152 liters. The clearance of mometasone furoate is not well understood, but is likely close to 90 liters/hour. Metabolism/Metabolites Mometasone furoate is primarily metabolized in the liver via cytochrome P450 3A4, producing several metabolites. These metabolites include free mometasone and 6-β-hydroxymometasone furoate. Biological Half-Life The terminal half-life of the inhaled dose is approximately 5 hours, but other sources have reported 5.8 hours.

Protein Binding
98% to 99% (in vitro concentrations of 5 to 500 ng/mL). 441336 Rats: Subcutaneous LD50 300 mg/kg. Lung, pleural cavity, or respiration: Respiratory depression. Kiso to Rinsho Clinical Report, 24(4203), 1990. 441336 Mice: Subcutaneous LDLo 1 gm/kg. Kiso to Rinsho Clinical Report, 24(4203), 1990.

[1]. Use of Mometasone furoate in prolonged treatment of experimental spinal cord injury in mice: A comparative study of three different glucocorticoids. Pharmacol Res. 2015 Sep;99:316-28.

[2]. https://go.drugbank.com/drugs/DB14512.

Mometasone furoate is a 2-furoate ester belonging to the steroidal ester, 11β-hydroxysteroid, 20-oxosteroid, organochlorine compound, and 3-oxo-Δ⁹Δ⁴steroid classes. It possesses anti-inflammatory and anti-allergic effects, functions of which are related to mometasone. Mometasone furoate is a corticosteroid used to treat asthma, rhinitis, and certain skin conditions. Its binding affinity to glucocorticoid receptors is 22 times that of dexamethasone and higher than many other corticosteroids. Mometasone furoate is available in dry powder inhalers, nasal sprays, and ointments for various indications. Mometasone furoate is the furoate ester form of mometasone, a synthetic topical glucocorticoid receptor (GR) agonist with anti-inflammatory, antipruritic, and vasoconstrictive effects. After administration, mometasone binds to cytoplasmic GR, subsequently activating GR-mediated gene expression. This leads to the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Specifically, mometasone appears to induce the expression of phospholipase A2 inhibitory protein, thereby controlling the release of the inflammatory precursor arachidonic acid from the phospholipase membrane by phospholipase A2. A pregnadiene glycol derivative with anti-allergic and anti-inflammatory effects, it is used to treat asthma and allergic rhinitis. It can also be used as a topical treatment for skin conditions. See also: mometasone (containing active ingredient); formoterol fumarate; mometasone furoate (ingredient); florfenicol; mometasone furoate; terbinafine (ingredient)... See more...

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Drug Indications
Inhaled mometasone furoate is indicated for asthma prevention in patients aged 4 years and older. Topical mometasone furoate ointment is indicated for the treatment of dermatitis and pruritus in patients aged 2 years and older. Mometasone furoate nasal spray is available in both over-the-counter (OTC) and prescription formulations. Over-the-counter mometasone furoate nasal spray is indicated for the treatment of upper respiratory tract allergy symptoms (such as runny nose and sneezing) in patients aged 2 years and older. This prescription drug is indicated for the treatment of chronic sinusitis with nasal polyps in patients aged 18 years and older, and for the treatment and prevention of seasonal allergic rhinitis in patients aged 12 years and older. It is also approved for use in combination with olopatadine for the treatment of symptoms of seasonal allergic rhinitis in patients aged 12 years and older.
FDA Label
Seasonal and Perennial Allergic Rhinitis

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Mechanism of Action
In asthma, mometasone furoate is thought to inhibit mast cells, eosinophils, basophils, and lymphocytes. There is also evidence that it inhibits histamine, leukotrienes, and cytokines. Corticosteroids diffuse across the cell membrane into the cytoplasm, where they bind to glucocorticoid receptors to exert their activity. Compared to other corticosteroids, mometasone furoate has a particularly high receptor affinity, 22 times higher than dexamethasone. The binding of mometasone furoate to glucocorticoid receptors causes a conformational change in the receptor, dissociating it from its molecular chaperone and translocating it into the cell nucleus. Once the receptor reaches the cell nucleus, it dimers and binds to DNA sequences called glucocorticoid response elements, thereby increasing the expression of anti-inflammatory molecules or inhibiting the expression of pro-inflammatory molecules (such as interleukins 4 and 5). Mometasone furoate can also reduce inflammation by blocking transcription factors such as activator protein-1 and nuclear factor-κB (NF-κB).

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Pharmacodynamics
Mometasone is a synthetic corticosteroid with an affinity for glucocorticoid receptors that is 22 times greater than that of dexamethasone. Mometasone furoate also has a lower affinity for mineralocorticoid receptors than natural corticosteroids, making its action more selective. Mometasone furoate can diffuse across the cell membrane and activate signaling pathways responsible for reducing inflammation.

C27H30CL2O6

521.43

520.14

C, 62.19; H, 5.80; Cl, 13.60; O, 18.41

83919-23-7

Mometasone furoate-d3; 141646-00-6 (furoate hydrate) 105102-22-5 (Mometasone)

441336

White to off-white solid powder

1.4±0.1 g/cm3

655.5±55.0 °C at 760 mmHg

218-220°C

350.2±31.5 °C

0.0±2.1 mmHg at 25°C

1.604

4.27

113.02

1

6

5

35

1020

8

WOFMFGQZHJDGCX-ZULDAHANSA-N

InChI=1S/C27H30Cl2O6/c1-15-11-19-18-7-6-16-12-17(30)8-9-24(16,2)26(18,29)21(31)13-25(19,3)27(15,22(32)14-28)35-23(33)20-5-4-10-34-20/h4-5,8-10,12,15,18-19,21,31H,6-7,11,13-14H2,1-3H3/t15-,18+,19+,21+,24+,25+,26+,27+/m1/s1

(8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-17-(2-chloroacetyl)-11-hydroxy-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 furan-2-carboxylate

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.79 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.79 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。