Figure 1.
Chemical structures and activities of the CD36 inhibitors AP 5055, AP 5258 and the negative analog AP5156.
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.
Figure 2.
Anti-CD36 activity of AP5055 (dark) and AP5258 (grey) on CD36-HEK cells.
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.
Figure 3.
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.
Figure 4.
Protection against atherosclerosis.
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.
Figure 5.
Reduction of plasma triglycerides.
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).
Figure 6.
Effect of CD36 inhibitors on insulin resistance.
A: Effect of AP5055 (1 mg/kg), on the glucose level and the glucose tolerance in the DKO mice, B: effect of AP5055 and AP 5258 on the plasma glucose in a ZDF rat (40 mg/kg, 3 w, n = 8).
Figure 7.
Effect of CD36 inhibitor on the metabolic syndrome parameters.
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.
Figure 8.
Reduction of FA intestinal transit.
Oral administration of anti-CD36 inhibitor reduces post prandial HTTG following a gastric olive oil challenge. A: kinetics of the TG intestinal transit in the plasma in control animals or treated animals (AP5258, 50 mg/kg n = 12), B: Dose dependent effect on Plasma TG (n = 3).
Table 1.
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.