Animal experiment:

Atherosclerosis studies are conducted in F1 hybrid C57BL/6×DBA/1 Ldlr+/- mice fed the Paigen diet, which is high-fat/cholesterol/bile salt diet containing 1.25% cholesterol, 7.5% cocoa butter, and 0.5% cholic acid. For 18 weeks, the mice are put on the Paigen diet with or without ITX5061 at 0.037 %. CETP expression is induced by injection of adeno-associated virus (AAV)8 TBG human CETP vector two weeks before starting the Paigen diet. Doses of virus are given by IP injection[1].

ITX5061 is a type II inhibitor of p38 MAPK and also an antagonist of scavenger receptor B1 (SR-B1).

ITX5061 is a type II inhibitor of p38 MAPK and also an antagonist of scavenger receptor B1 (SR-B1). Treatment of ITX5061 (30 mg/kg/day) for mice results in a 50% increase in HDL-C levels compare to baseline. ApoA-I levels are moderately (+15 %) but significantly increased in ITX5061-treated HuAITg mice, compare to mice receive vehicle. ITX5061 significantly decreases HDL-CE catabolism with an FCR of 1.86±0.40 pools/d vs 2.47±0.26 pools/d in the control group (P<0.05), while calculated production rates are identical in both groups (129±24 μg/g/d vs 129±16 μg/g/d). Moreover, accumulation of [3H] CE in the liver is significantly lower in ITX5061-treated mice indicating that increased HDL-CE levels are due to reduced uptake by the liver[1].

[1]. Masson D, et al. Increased HDL cholesterol and apoA-I in humans and mice treated with a novel SR-BI inhibitor. Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2054-60.