Cilomilast (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

, codenamed SB-207,499, proposed trade name Ariflo) is a drug which was developed for the treatment of respiratory disorders such as

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, c ...

and

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

(COPD). It is orally active and acts as a selective phosphodiesterase-4 inhibitor.

Phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many o ...

(PDE) inhibitors, such as

theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...

, have been used to treat COPD for centuries; however, the clinical benefits of these agents have never been shown to outweigh the risks of their numerous adverse effects. Four clinical trials were identified evaluating the efficacy of cilomilast, the usual randomized, double-blind, and placebo-controlled protocols were used. It showed reasonable efficacy for treating COPD, but side effects were problematic and it is unclear whether cilomalast will be marketed, or merely used in the development of newer drugs. Cilomilast is a second-generation PDE4 inhibitor with

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as ...

effects that target

bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Causes The condition has a number of causes, the most common bei ...

mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...

hypersecretion, and airway remodeling associated with COPD.

History

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

(GSK) filed for drug approval with the U.S. FDA at the end of 2002 and in January 2003 with the

European Medicines Evaluation Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMEA). In October 2003 the FDA issued an approvable letter for use of cilomilast in maintenance of lung function in COPD patients poorly responsive to salbutamol, despite an earlier decision by the FDA advisory panel to reject approval. The rejection was based on concerns over the efficacy of the agent, as well as gastrointestinal side effects. Before issuing final approval, however, the FDA requested additional efficacy and safety data. The development of the drug was finally abandoned by GSK.

Synthesis

References

{{Phosphodiesterase inhibitors Abandoned drugs Carboxylic acids Nitriles Catechol ethers PDE4 inhibitors