| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
| 体外研究 (In Vitro) |
罗氟司特是大多数测试的 PDE4 剪接变体的亚纳摩尔抑制剂，并且对 PDE4 以外的 PDE 酶没有影响。除了 PDE4C（4C1，IC50=3 nM；4C2，IC50= 4.3 nM）外，其抑制效力稍差，它没有表现出 PDE4 同工型选择性 [2]。罗氟司特是一种强效且特异性的 PDE4 抑制剂。在浓度高达 10,000 倍时，罗氟司特不会影响其他 PDE 同工酶，例如 PDE1、PDE2、PDE3 或 PDE5。这使其成为 PDE4 的单选择性抑制剂。罗氟司特抑制人中性粒细胞的活性。罗氟司特可阻止单核细胞衍生的树突状细胞合成 TNFα。 rolfumilast 抑制细胞因子合成和 CD4+ T 细胞增殖。 rolumilast 在 7 nM 的效力 (IC30) 下可抑制高达 60% 的增殖 [3]。
|
||
|---|---|---|---|
| 体内研究 (In Vivo) |
对动物的研究表明，使用罗氟司特可减少小鼠、大鼠或豚鼠短期接触烟草烟雾后支气管肺泡灌洗液中中性粒细胞的积聚；此外，它还能消除暴露于烟草烟雾七个月的大鼠肺实质中炎症细胞的浸润[2]。在 pIgR 中，rolumilast 可以预防 COPD 的进展？*？老鼠。 9 个月大的 WT 或 pIgR 用于这些研究？*？三个月内，小鼠接受 100 μg 罗氟司特 (5 μg/g) 或载体（4% 甲基纤维素，1.3% PEG400）口服强饲治疗。大约12个月大时，肺部被摘除。当罗氟司特给予小鼠时，轻微气道壁重塑并未像媒介物处理的 pIgR-/- 动物那样进展。令人惊讶的是，12 个月大的 pIgR 接受了罗鲁司特？*？与9个月大的pIgR相比，小鼠的肺气肿指数较低。*？正如小鼠所证明的那样，在这种情况下，罗氟司特不仅可以阻止肺气肿的发展。似乎有助于解决整个肺气肿过程中肺实质的肺气肿损失[4]。
|
||
| 动物实验 |
|
||
| 药代性质 (ADME/PK) |
Absorption, Distribution and Excretion
After a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours, while in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged. Applied topically, the mean systemic exposure for roflumilast and its N-oxide metabolite in adults was 72.7 ± 53.1 and 628 ± 648 h∙ng/mL, respectively. The mean systemic exposure for roflumilast and its N-oxide metabolite in adolescents was 25.1 ± 24.0 and 140 ± 179 h∙ng/mL, respectively. Roflumilast is excreted 70% in the urine as roflumilast N-oxide. Following a single oral dose of 500 mcg, the volume of distribution of roflumilast is approximately 2.9 L/kg. Plasma clearance of roflumilast following short-term intravenous infusion is approximately 9.6 L/h. Metabolism / Metabolites Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2. The N-oxide metabolite is less potent than its parent drug in regards to PDE4 inhibition, but its plasma AUC is approximately 10-fold greater. Biological Half-Life Following oral administration, the plasma half-lives of roflumilast and roflumilast N-oxide are 17 hours and 30 hours, respectively. |
||
| 毒性/毒理 (Toxicokinetics/TK) |
Hepatotoxicity
In preregistration studies, roflumilast was not associated with serum enzyme elevations or with episodes of clinically apparent liver injury. Since approval of roflumilast, there have been no published reports of hepatotoxicity, and the product label does not mention liver injury as an adverse event. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of roflumilast in nursing mothers. The drug and its metabolite are more than 97% bound to plasma proteins, so amounts in milk are likely to be very low. However, the manufacturer and some experts recommend that the oral drug should not be used by women who are nursing. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, respectively. |
||
| 参考文献 |
|
||
| 其他信息 |
Pharmacodynamics
Roflumilast and its active metabolite, roflumilast N-oxide, increase cyclic adenosine-3′, 5′-monophosphate (cAMP) in affected cells by inhibiting PDE4. They are highly selective for PDE4 and are effectively inactive against PDEs 1, 2, 3, 5, and 7. |
| 分子式 |
C17H14CL2F2N2O3
|
|---|---|
| 分子量 |
403.2075
|
| 精确质量 |
402.034
|
| CAS号 |
162401-32-3
|
| 相关CAS号 |
Roflumilast N-oxide;292135-78-5;Roflumilast-d4 N-Oxide;1794760-31-8;Roflumilast Impurity E;1391052-76-8;Roflumilast-d4;1398065-69-4;Roflumilast-d3;1189992-00-4
|
| PubChem CID |
449193
|
| 外观&性状 |
White to off-white solid powder
|
| 密度 |
1.5±0.1 g/cm3
|
| 沸点 |
430.6±45.0 °C at 760 mmHg
|
| 熔点 |
158°C
|
| 闪点 |
214.2±28.7 °C
|
| 蒸汽压 |
0.0±1.0 mmHg at 25°C
|
| 折射率 |
1.604
|
| LogP |
4.84
|
| tPSA |
60.45
|
| 氢键供体(HBD)数目 |
1
|
| 氢键受体(HBA)数目 |
6
|
| 可旋转键数目(RBC) |
7
|
| 重原子数目 |
26
|
| 分子复杂度/Complexity |
475
|
| 定义原子立体中心数目 |
0
|
| InChi Key |
MNDBXUUTURYVHR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)
|
| 化学名 |
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
|
| 别名 |
Daliresp; BY217; BY-217; B 9302-107;BYK 20869;B-9302-107;APTA 2217, B9302-107, BY 217, BYK-20869; BYK20869; Daxas;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 溶解度 (体外实验) |
|
|||
|---|---|---|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (6.20 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 储备液加入900 μL 玉米油中，混合均匀。 配方 2 中的溶解度: 30% PEG400+0.5% Tween80+5% propylene glycol:30 mg/mL 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。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4801 mL | 12.4005 mL | 24.8010 mL | |
| 5 mM | 0.4960 mL | 2.4801 mL | 4.9602 mL | |
| 10 mM | 0.2480 mL | 1.2400 mL | 2.4801 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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) 。
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05684744 | Completed | Drug: Roflumilast Drug: Methotrexate |
Psoriasis | Cairo University | January 9, 2023 | Phase 2 Phase 3 |
| NCT04322929 | Recruiting | Drug: Roflumilast Oral Tablet | Non-cystic Fibrosis Bronchiectasis | The University of Hong Kong | November 12, 2020 | Phase 2 |
| NCT04549870 | Completed | Drug: Roflumilast | Psoriasis | Bispebjerg Hospital | January 1, 2021 | Phase 2 |
| NCT04108377 | Terminated | Drug: Roflumilast Drug: Placebo |
Asthma | University of California, Davis | January 21, 2019 | Phase 1 |
FCPR-16
Mardepodect盐酸盐
盐酸阿那格雷
己酮可可碱
InvivoChem的所有产品仅用于作科学研究，不面向患者销售
Copyright 2020 InvivoChem LLC | All Rights Reserved 粤ICP备20063088号-1
COA
粤公网安备 44011102003439号
