DP(2) receptor antagonists in development.
BACKGROUND
In asthmatic lung, allergen challenge leads to the production of large quantities of (prostaglandin D(2)) PGD(2) which both contracts human airway tissue and stimulates an inflammatory response. The identification of PGD(2) as the cognate ligand for a second specific receptor, the DP(2) receptor and the limited inhibition of its pro-inflammatory effects by TP or DP(1) receptor antagonists provide the stimulus to identify, and characterize, selective DP(2) antagonists. This has led to considerable interest in the development of such agents, stimulated by promising initial clinical data.


METHODS
The 10 DP(2) 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.


RESULTS
A comprehensive overview of the state of the art in the development of DP(2) antagonists for the treatment of asthma, and knowledge of the companies which are currently actively seeking to develop such agents.


CONCLUSIONS
Considerable progress has been made in the development of selective DP(2) 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.
Norman
Peter
P
Norman Consulting, Burnham, Bucks, UK. peter.norman2@btinternet.com
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D015195:Drug Design; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D015230:Prostaglandin D2 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor