DP₂ receptor antagonists in development

Abstract

Importance of the field: In asthmatic lung, allergen challenge leads to the production of large quantities of (prostaglandin D₂) PGD₂ which both contracts human airway tissue and stimulates an inflammatory response. The identification of PGD₂ as the cognate ligand for a second specific receptor, the DP₂ receptor and the limited inhibition of its pro-inflammatory effects by TP or DP₁ receptor antagonists provide the stimulus to identify, and characterize, selective DP₂ antagonists. This has led to considerable interest in the development of such agents, stimulated by promising initial clinical data.

Areas covered in this review: The 10 DP₂ antagonists reported to be in clinical development are considered in as much detail as possible from available information. Reported preclinical efforts are also considered and contrasted to more advanced agents.

What the reader will gain: A comprehensive overview of the state of the art in the development of DP₂ antagonists for the treatment of asthma, and knowledge of the companies which are currently actively seeking to develop such agents.

Take home message: Considerable progress has been made in the development of selective DP₂ antagonists and initial indications are that they could prove a useful new option in the treatment of asthma. More comprehensive clinical results that will shortly become available will further clarify their therapeutic potential and also indicate the possibility of their use in the treatment of chronic obstructive pulmonary disease.

Keywords::

• asthma
• COPD
• DP₁ receptor
• DP₂ receptor
• inflammation
• PGD₂
• TXA₂

Notes

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