Roflumilast

Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor. Due to its selective inhibition of the PDE4 isoenzyme in lung cells, roflumilast is indicated for the management of chronic obstrtuctive pulmonary disease (COPD) exacerbations. Treatment with Roflumilast is associated with an increase in psychiatric adverse reactions, including suicide and suicidal attempts. (In Vitro) :Roflumilast does not affect PDE enzymes apart from PDE4, and is a subnanomolar inhibitor of most PDE4 splicing variants tested. It showed no PDE4 subtype selectivity apart from PDE4C (4C1, IC50=3 nM; 4C2, IC50=4.3 nM), which is inhibited with a slightly lower potency. Roflumilast is a potent and selective PDE4 inhibitor. Roflumilast is a monoselective PDE4 inhibitor since it does not affect other PDE isoenzymes, including PDE1, PDE2, PDE3, and PDE5 up to 10,000-fold higher concentrations. Roflumilast inhibits human neutrophil functions. Roflumilast inhibits TNFα synthesis in monocyte-derived dendritic cells. Rolfumilast inhibits proliferation and cytokine synthesis in CD4+ T cells. Proliferation is inhibited to a maximum of about 60% by Roflumilast with a potency (IC30) of 7 nM. (In Vivo) :Animal studies with Roflumilast demonstrated that it reduced the accumulation of neutrophils in bronchoalveolar lavage fluid following short-term exposure of guinea pigs, mice or rats to tobacco smoke, and following exposure of rats to a combination of tobacco smoke and bacterial lipopolysaccharide, and abolished the lung parenchymal influx of inflammatory cells seen in rats exposed to tobacco smoke for 7 months. Roflumilast blocks COPD progression in pIgR / mice. For these studies, 9-month-old WT or pIgR / mice are treated daily by oral gavage with 100 μg of Roflumilast (5 μg/g) or vehicle (4% methylcellulose, 1.3% PEG400) for 3 months and lungs are harvested at 12 months of age. Unlike pIgR / mice treated with vehicle, mice treated with Roflumilast had no progression of small airway wall remodelling after starting treatment. Strikingly, 12-month-old pIgR / mice treated with Roflumilast had reduced indices of emphysema compared with 9-month-old pIgR / mice, indicating that Roflumilast not only blocks progression of emphysema in this model but apparently facilitates some resolution of the emphysematous destruction of lung parenchyma.

162401-32-3

B 9302-107 | BY 217 | BYK 20869 | Daxas

Pharmacology & Drug Discovery

>98% (HPLC)

Ethanol: 15 mg/mL (37.2 mM) ; DMSO: 81 mg/mL (200.88 mM)

O=C (NC1=C (Cl) C=NC=C1Cl) C2=CC=C (OC (F) F) C (OCC3CC3) =C2

C17H14Cl2F2N2O3

403.21

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.