Roflumilast

製品コードS2131 バッチS213102

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 15 mg/mL (37.2 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 ロフルミラストは、無細胞アッセイにおいてIC50が0.2～4.3 nMのPDE4の選択的阻害剤です。
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.

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. 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.

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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