Chemical structures and activities of the CD36 inhibitors AP 5055, AP 5258 and the negative analog AP5156.

<p>Dose dependent inhibition of ox-LDL uptake and accumulation by THP1 cells at 37°C. Uptake was measured as the cyanin3 labeled ox-LDL uptake at constant cell number.</p

Inhibition of ppTG in the plasma at four hours following the olive oil gavage following administration of 50 mg/kg of active (AP5055, AP5258) or inactive (AP5156) analogues.

<p>Inhibition of ppTG in the plasma at four hours following the olive oil gavage following administration of 50 mg/kg of active (AP5055, AP5258) or inactive (AP5156) analogues.</p

Reduction of plasma triglycerides.

<p>Comparative effect of CD36 inhibitors on the plasma concentrations of TG in different rat models, A: Dose dependent reduction in a fructose fed rat, AP5055 was administrated at different doses for 3 w (n = 12), B: AP5258 was administrated to diabetic ZDF rats (C = Control, T = Treated) for a period of 2w at 10 mg/kg (n = 8).</p

Anti-CD36 activity.

<p>Effect of AP5055 on the molecular interaction between CD36 and ox-LDL using CD36-HEK and wild type (wt) cells at 4°C. A: effect on the electrophoretic mobility of ox-LDL, B: Affinity crosslinking of ox-LDL to membrane expressed CD36, biotinylated ox-LDL were cross linked at 4°C, the ox-LDL complex was immunoprecipitated with an anti ox-LDL antibody and complex-associated CD36 was detected on immunoblot, using an anti CD36 antibody.</p

Anti-CD36 activity of AP5055 (dark) and AP5258 (grey) on CD36-HEK cells.

<p>Non transfected cells (wt), were used as control: A: ox-LDL uptake at 37°C, B: Palmitate uptake at 37°C, C: typical inhibition of ox-LDL binding at 4°C, D: dose dependent inhibition of AP 5055 and AP5258 on ox-LDL binding, AP5156 used as negative control had no effect (hatched bar), E: Comparative inhibition of ox-LDL binding by AP5055 and AP5258 at different ox-LDL concentrations.</p

Protection against atherosclerosis.

<p>Effect of AP 5055 on the development of atherosclerosis in double LDL-R and Leptin deficient mice (DKO). A: lipid deposition in the aorta, B: plaque volume, C: plasma TG concentration.</p

Effect of CD36 inhibitor on the metabolic syndrome parameters.

<p>A: effect of AP5258 on OGT, B: Effect of 5258 on insulin sensitivity, C: Effect of AP5055 on plasma glucose, D: Effect of 5055 on the plasma concentration of HbAc1.</p