Darapladib.
BACKGROUND
Atherosclerosis is an inflammatory-immune mediated disease process. Plaque rupture is responsible for the clinical events of ischemic death, myocardial infarction, acute coronary syndromes and ischemic strokes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) seems to play a major role in the development of such high-risk lesions, in both the coronary and carotid arteries. Darapladib is a selective inhibitor of Lp-PLA(2).


METHODS
An overview of darapladib by reviewing the studies (1990 - 2009) that have provided the rationale for the development of darapladib; and a discussion of its potential merit as a new therapeutic drug to target high-risk atherosclerosis.


RESULTS
The reader should gain an understanding of the importance of inflammation during atherogenesis as well as of the biology of Lp-PLA(2) and its proatherogenic role. Additional insights will be gained into the role of selective inhibitors of Lp-PLA(2) as new therapeutic agents.


CONCLUSIONS
Darapladib is a selective inhibitor of Lp-PLA(2) and represents a new class of therapeutic agents that target inflammation to treat high-risk atherosclerosis.
Bui
Quang T
QT
University of Pennsylvania, Hospital of the University of Pennsylvania, Cardiovascular Institute, Cardiovascular Division, Philadelphia, PA 19104, USA.
Wilensky
Robert L
RL
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology; D001547:Benzaldehydes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001547:Benzaldehydes; D010091:Oximes; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides