NVP-ABE171, a selective PDE4D inhibitor for the treatment of airway inflammatory disease

Sunday November 22 2009 | Biotechnology feed | All feeds

NVP-ABE171, a selective PDE4D inhibitor for the treatment of airway inflammatory disease

There is a pressing need to develop new treatments for chronic obstructive pulmonary disease (COPD), as no currently available drug therapy reduces the relentless progression of the diseases, chronic obstructive bronchitis and emphysema, falling under the umbrella of COPD. World-wide, 600 million people suffer from COPD, with some three million dying from the disease each year representing a globally market of US$2.8 billion US. There is a particular need to develop drugs that control the underlying inflammatory and destructive processes that cause COPD. A growing recognition of the global importance and rising prevalence of COPD and the absence of effective therapies explain why our recent state of the art review of this disease (click here for access) has received a high level of industrial interest. This report overviews most current targets of COPD including PDE4 inhibitors and profiles leaders of this field including Roflumilast, Arofylline and Cilomilast. More recently TherapeuticAdvances reports the development of Novartis' NVP-ABE171. This PDE4 inhibitors was 40-fold more potent than Arofylline and furthermore it displayed greater selectivity for the PDE4D isoform, a feature likely to contribute to an improved side-effect profile. NVP-ABE171 inhibited the eosinophil and neutrophil oxidative burst, the release of cytokines by T cells, and the tumor necrosis factor-alpha release from monocytes, in the nanomolar range. In vivo, NVP-ABE171 inhibited airway neutrophil and eosinophil infiltration and activation at 0.1-3 mg/kg, demonstrating around 100-fold greater efficacy than Arofylline with respect to some of these parameters. NVP-ABE171 had a duration of action of more than 24 h and thus represents a highly attractive therapeutic candidate for COPD as well as for other chronic airway diseases such as asthma.

Link to journal abstract:

Pharmacological profile of a novel phosphodiesterase 4 inhibitor, 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridin-6-yl)-benzoic acid (NVP-ABE171), a 1,7-naphthyridine derivative, with anti-inflammatory activities.

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