Roflumilast

製品コードS2131 バッチS213103

印刷

化学情報

Chemical Structure Synonyms APTA 2217, B9302-107, BY 217, BYK 20869 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H14Cl2F2N2O3
分子量 403.21 CAS No. 162401-32-3
Solubility (25°C)* 体外 DMSO 81 mg/mL (200.88 mM)
Ethanol 21 mg/mL (52.08 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Roflumilast is a selective inhibitor of PDE4 with IC50 of 0.2-4.3 nM in a cell-free assay.
in vitro

Roflumilast displays anti-inflammatory and immunomodulatory in vitro. This compound inhibits LTB4 synthesis in human neutrophil with IC50 of 2 nM. It inhibits fMLP-stimulated ROS formation as luminol-enhanced CL in human neutrophils or eosinophils with IC35 of 4 nM, and 7 nM, repectively. The chemical inhibits LPS-stimulated TNF-α synthesis in monocytes with IC40 of 21 nM. It inhibits TNF-α synthesis in monocyte-derived dendritic cells with IC20 of 5 nM. This compound inhibits anti-CD3 and anti-CD28 antibody-stimulated proliferation of CD4+ T cells with IC30 of 7 nM. It inhibits anti-CD3 and anti-CD28 antibody-stimulated synthesis of IL-2, IL-4, IL-5, and IFN-v in CD4+ T cells with IC20 of 1 nM, IC30 of 7 nM, IC25 of 13 nM, and IC35 of 8 nM, respectively. [2]
in vivo

Roflumilast is activity against pulmonary inflammatory response related to COPD in animal model. This compound (5 mg/kg/day) induces reduction of neutrophils, macrophages, DC, B-cells, CD4+ T cells, CD8+ T cells in the lung of mice exposed to tobacco smoke for 7 month by 78%, 82%, 48%, 100%, 98%, and 88%, respectively. [3] It is an efficient inhibitor of lung fibrotic remodeling. This chemical dose-dependently diminishes total lung hydroxyproline after bleomycin, attaining about 47% inhibition at 5 mg/kg/day, paralleled by a reduction in lung αI(I) collagen transcripts and fibrotic lesions. It reduces oxidative stress in vivo. This compound (5 mg/kg/day) moderately reduces an increase in BAL fluid lipid hydroperoxides measured at day 14 after intratracheal bleomycin administration in mice. [4]

プロトコル(参考用のみ)

キナーゼアッセイ PDE activity assay
The assay mixture contains 50 mM Tris (pH 7.4), 5 mM MgCl2, 0.5 μM cAMP or cGMP, and [3H]cAMP or [3H]cGMP (about 30,000 cpm/assay), the indicated concentration of the inhibitor and an aliquot of the enzyme solution at a final assay volume of 200 μL.Stock solutions of the compounds are diluted 1:100 (v/v) in the Tris buffer; appropriate dilutions are prepared in 1% (v/v) DMSO/Tris buffer, which are diluted 1:2 (v/v) in the assays to obtain the desired final concentrations of the inhibitors at a DMSO concentration of 0.5% (v/v). DMSO itself affects none of the PDE activity.After preincubation for 5 min at 37 ℃, the reaction is started by the addition of substrate (cAMP or cGMP) and the assays are incubated for further 15 min at 37 ℃. Then 50 μL of 0.2 N HCl is added to stop the reaction and the assays are left on ice for about 10 min. Following incubation with 25 μg of 5’-nucleotidase for 10 min at 37 ℃, the assays are loaded on QAE Sephadex A-25 (1 mL of bed volume in Poly-Prep chromatography column). The columns are eluted with 2 mL of 30 mM ammonium formate (pH 6.0) and the eluate is counted for radioactivity. Results are corrected for blank values (measured in the presence of denatured protein) that are below 5% of total radioactivity. The amount of cyclic nucleotides hydrolyzed does not exceed 30% of the original substrate concentration.

参考

  • https://pubmed.ncbi.nlm.nih.gov/20381629/
  • https://pubmed.ncbi.nlm.nih.gov/11259554/
  • https://pubmed.ncbi.nlm.nih.gov/18755021/
  • https://pubmed.ncbi.nlm.nih.gov/19154443/

カスタマーフィードバック

Data from [J Mass Spectrom, 2012, 47, 1612-1619 ]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

PDE4D inhibition ameliorates cardiac hypertrophy and heart failure by activating mitophagy [ Redox Biol, 2025, 81:103563] PubMed: 40015131
Roflumilast Attenuates Microglial Senescence and Retinal Inflammatory Neurodegeneration Post Retinal Ischemia Reperfusion Injury Through Inhibiting NLRP3 Inflammasome [ Invest Ophthalmol Vis Sci, 2024, 65(12):38] PubMed: 39446353
Functional rescue of CFTR in rectal organoids from patients carrying R334W variant by CFTR modulators and PDE4 inhibitor Roflumilast [ Respir Investig, 2024, 62(3):455-461] PubMed: 38547757
PDE4D binds and interacts with YAP to cooperatively promote HCC progression [ Cancer Lett, 2022, 541:215749] PubMed: 35597479
Long-Acting β2 Adrenergic Receptor Agonist Ameliorates Imiquimod-Induced Psoriasis-Like Skin Lesion by Regulating Keratinocyte Proliferation and Apoptosis [ Front Pharmacol, 2022, 13:865715] PubMed: 35795567
Estimulantes y Activadores de la Guanilato Ciclasa en el Tratamiento del Asma y la Enfermedad Pulmonar Obstructiva Crónica [ University of Valencia, 2022, ] PubMed: None
Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25+ /CD54+ NK cells [ EMBO Rep, 2021, e51329] PubMed: 33480074
Roflumilast prevents ischemic stroke-induced neuronal damage by restricting GSK3β-mediated oxidative stress and IRE1α/TRAF2/JNK pathway [ Free Radic Biol Med, 2021, 163:281-296] PubMed: 33359910
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2 [ Mol Cell, 2020, 80(6):1104-1122.e9] PubMed: 33259812
Hyperinsulinemia promotes heterologous desensitization of β2 adrenergic receptor in airway smooth muscle in obesity. [ FASEB J, 2020, 10.1096/fj.201800688RR] PubMed: 31960515

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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