product name Roflumilast
Description: Roflumilast is a highly potent, selective, and long-acting inhibitor of PDE4 with IC50 of 0.2-4.3 nM in a cell-free assay. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs such as asthma, and chronic obstructive pulmonary disease (COPD). In vitro studies show that roflumilast inhibits the production of inflammatory mediators in a variety of human immune cells, suggesting a role for reducing COPD-related inflammation.
References: Pulm Pharmacol Ther. 2010 Aug;23(4):235-56; J Pharmacol Exp Ther. 2001 Apr;297(1):267-79.
403.21
Formula
C17H14Cl2F2N2O3
CAS No.
162401-32-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 81 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: 15 mg/mL (37.2 mM)
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
Synonyms
APTA 2217, B9302-107, BY 217, BYK 20869
other peoduct :
| In Vitro |
In vitro activity: Roflumilast displays anti-inflammatory and immunomodulatory in vitro. Roflumilast inhibits LTB4 synthesis in human neutrophil with IC50 of 2 nM. Roflumilast inhibits fMLP-stimulated ROS formation as luminol-enhanced CL in human neutrophils or eosinophils with IC35 of 4 nM, and 7 nM, repectively. Roflumilast inhibits LPS-stimulated TNF-α synthesis in monocytes with IC40 of 21 nM. Roflumilast inhibits TNF-α synthesis in monocyte-derived dendritic cells with IC20 of 5 nM. Rolfumilast inhibits anti-CD3 and anti-CD28 antibody-stimulated proliferation of CD4+ T cells with IC30 of 7 nM. Rolfumilast 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. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Roflumilast is activity against pulmonary inflammatory response related to COPD in animal model. Roflumilast (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. Roflumilast is an efficient inhibitor of lung fibrotic remodeling. Roflumilast 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. Roflumilast reduces oxidative stress in vivo. Roflumilast (5 mg/kg/day) moderately reduces an increase in BAL fluid lipid hydroperoxides measured at day 14 after intratracheal bleomycin administration in mice. |
| Animal model | COPD Mice model |
| Formulation & Dosage | 5 mg/kg |
| References | BMC Pulm Med. 2008 Aug 28;8:17. doi: 10.1186/1471-2466-8-17; Br J Pharmacol. 2009 Feb;156(3):534-44. |
