Plaque rupture is responsible for the clinical events of ischemic death, myocardial infarction, acute coronary syndromes and ischemic strokes. Lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2.
In vitro: Darapladib potently inhibited Lp-PLA2 with an IC50 of 270 pM. A lack of selectivity against other secretory PLA2s postulated to play a role in atherogenesis had been demonstrated. The percentage inhibition achieved when 1 μM darapladib was evaluated against human secretory PLA2s IIA, V and X, was 0, 0 and 8.7%, respectively .
In vivo: Inhibition of lp-PLA2 by darapladib led to attenuation of inflammation in vivo and decreased plaque formation in ApoE-deficient mice, suggesting an anti-atherogenic role during the progression of atherosclerosis .
Clinical trial: Darapladib produced sustained inhibition of plasma Lp-PLA2 activity in patients receiving intensive atorvastatin therapy. IL-6 and hs-CRP changes after 12 weeks of darapladib 160 mg suggested a possible reduction in inflammatory burden .
 Bui QT, Wilensky RL. Darapladib. Expert Opin Investig Drugs. 2010;19(1):161-8.
 Wang WY, Zhang J, Wu WY, Li J, Ma YL, Chen WH, Yan H, Wang K, Xu WW, Shen JH, Wang YP. Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in ApoE-deficient mice. PLoS One. 2011;6(8):e23425.
 Mohler ER 3rd, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A; Darapladib Investigators. The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2008;51(17):1632-41.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||≥32.95 mg/mL in DMSO, ≥891 mg/mL in EtOH, <2.52 mg/mL in H2O|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Description||Darapladib (SB-480848) is a reversible inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with IC50 of 0.25 nM.|