| 规格 | 价格 | 库存 | 数量 |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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| 靶点 |
AZD5423 is >900-fold selective for other steroid hormone receptors and has significant affinity for the glucocorticoid receptor, with an IC50 of 0.9 nM in the radioligand human glucocorticoid receptor assay [1].
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| 体外研究 (In Vitro) |
AZD5423 对其他类固醇激素受体的选择性超过 900 倍，并且对糖皮质激素受体具有显着的亲和力，在放射性配体人糖皮质激素受体测定中的 IC50 为 0.9 nM [1]。
当前的临床研究文章未包含关于 AZD5423 的详细体外实验结果（例如基于细胞的实验、Western blot、PCR）。它引用了先前的工作，表明 AZD5423 似乎优先与某些辅因子（例如核受体相互作用蛋白1、核受体共激活因子1、过氧化物酶体增殖物激活受体γ共激活因子1α）相互作用，可能导致基因表达谱的改变。[2] |
| 体内研究 (In Vivo) |
在一项针对轻度过敏性哮喘受试者的随机、双盲、交叉研究中，每日一次吸入 AZD5423（300 µg）治疗7天，能显著减弱过敏原诱导的晚期哮喘反应（LAR）。LAR期间FEV1最大下降百分比在 AZD5423 300 µg组为-8.4%（SEM 1.6），75 µg组为-8.7%（SEM 1.7），而安慰剂组为-13.7%（SEM 2.3）。[2]
与安慰剂相比，AZD5423（300 µg）能显著减弱过敏原激发后24小时的气道高反应性（AHR）。从第1天到第7天，300 µg剂量组的乙酰甲胺激PC20显著改善。与安慰剂相比，75 µg剂量对过敏原诱导的PC20下降也显示出显著的抑制作用。[2] 两种剂量的 AZD5423（75 µg和300 µg）均能显著减弱过敏原诱导的痰嗜酸性粒细胞增多。与安慰剂相比，在过敏原激发后7小时，75 µg和300 µg剂量组的抑制率分别为61%和63%。在24小时，抑制率分别为34%和46%。与阳性对照布地奈德相比，300 µg剂量在24小时对痰嗜酸性粒细胞的减少作用也显著更强。[2] AZD5423 对早期哮喘反应（EAR）、其他痰炎症细胞（中性粒细胞、淋巴细胞）或循环白细胞无显著影响。[2] |
| 动物实验 |
The article references a previous rat model of pulmonary inflammation (Sephadex bead-induced, eosinophil-driven) where AZD5423 administered via dry-powder inhalation demonstrated a dose-dependent inhibition of lung inflammation. In the same model, thymic involution (decrease in thymus weight) was used to quantify systemic GR agonism. The ratio of systemic effect (ED25 for thymus involution) to anti-inflammatory potency (ED50 for lung edema) for AZD5423 was approximately fivefold improved compared to the reference inhaled corticosteroid budesonide. [2]
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| 药代性质 (ADME/PK) |
The pharmacokinetics of inhaled AZD5423 are characterized by rapid absorption from the lung and fast overall elimination. No consistent deviation from dose-proportional pharmacokinetics was observed, and no time-dependent pharmacokinetics were indicated. The accumulation ratio was low (≤1.5). [2]
Clearance data indicate that AZD5423 is a high hepatic extraction drug. [2] The major contribution to systemic availability comes from lung absorption, as the oral bioavailability of AZD5423 is low (approximately 3%). [2] |
| 毒性/毒理 (Toxicokinetics/TK) |
In the 7-day clinical study, AZD5423 (75 and 300 µg) was well-tolerated. There were no deaths, serious adverse events (AEs), or discontinuations due to AEs. The most common AEs were typical of inhaled therapies (e.g., headache, oropharyngeal pain). The lowest frequency of AEs was reported during the 300 µg treatment period. [2]
Treatment with AZD5423 did not significantly change serum concentrations of dehydroepiandrosterone sulfate or osteocalcin compared to placebo, suggesting no acute impact on the hypothalamic-pituitary-adrenal (HPA) axis or bone turnover markers in this short-term study. [2] The study duration was considered too short to properly evaluate the systemic effects characteristic of GR agonists. [2] |
| 参考文献 |
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| 其他信息 |
AZD5423 has been used in trials studying the basic science and treatment of Asthma, Bioavailability and AUC, and Chronic Obstructive Pulmonary Disease (COPD).
AZD5423 is an inhaled, nonsteroidal, potent, and selective glucocorticoid receptor modulator designed to provide the beneficial anti-inflammatory effects of conventional GR agonists while aiming to reduce adverse systemic effects. [2] The differential binding mode and cofactor interaction profile of AZD5423 compared to classical glucocorticosteroids may lead to an altered gene expression profile and potentially an improved therapeutic window. [2] This study demonstrates proof-of-concept for the efficacy of a nonsteroidal GR agonist in a human model of allergic asthma, showing attenuation of key features: late-phase bronchoconstriction, airway hyperresponsiveness, and eosinophilic inflammation. [2] |
| 精确质量 |
487.151
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|---|---|
| CAS号 |
1034148-04-3
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| PubChem CID |
24825740
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| 外观&性状 |
White to yellow solid powder
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| 密度 |
1.3±0.1 g/cm3
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| 沸点 |
573.8±50.0 °C at 760 mmHg
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| 闪点 |
300.8±30.1 °C
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| 蒸汽压 |
0.0±1.6 mmHg at 25°C
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| 折射率 |
1.574
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| LogP |
5.89
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| tPSA |
68.87
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| 氢键供体(HBD)数目 |
1
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| 氢键受体(HBA)数目 |
8
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| 可旋转键数目(RBC) |
7
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| 重原子数目 |
35
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| 分子复杂度/Complexity |
704
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| 定义原子立体中心数目 |
2
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| SMILES |
C[C@@H]([C@@H](C1=CC(=CC=C1)OC)OC2=CC3=C(C=C2)N(N=C3)C4=CC=C(C=C4)F)NC(=O)C(F)(F)F
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| InChi Key |
FCNQMDSJHADDFT-WNSKOXEYSA-N
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| InChi Code |
InChI=1S/C25H21F4N3O3/c1-15(31-24(33)25(27,28)29)23(16-4-3-5-20(12-16)34-2)35-21-10-11-22-17(13-21)14-30-32(22)19-8-6-18(26)7-9-19/h3-15,23H,1-2H3,(H,31,33)/t15-,23-/m0/s1
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| 化学名 |
2,2,2-Trifluoro-N-((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(3-methoxyphenyl)-2-propanyl)acetamide
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| 别名 |
AZD-5423; AZD 5423; AZD5423; UNII-641H0Q518W;
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
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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| 溶解度 (体外实验) |
DMSO : ~100 mg/mL (~205.15 mM)
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|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.08 mg/mL (4.27 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.08 mg/mL (4.27 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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。 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。 |
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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