Cholesterol is an important component of cell membrane. However, elevated level of serum cholesterol is a key risk factor for heart disease. Niemann-Pick C1-Like 1 (NPC1L1) is the crucial target involving in cholesterol cellar uptake. Ezetimibe is the first, and only, NPC1L1 inhibitor approved for the treatment of hypercholesterolemia through decreasing cholesterol absorption for nearly two decades. That means that the development of NPC1L1 inhibitors encounters much challenge, as well as offers exciting therapeutic opportunities. Substantial efforts have been undertaken to develop NPC1L1 inhibitors. The present review describes the mechanism of cholesterol transport by NPC1L1, highlights the development of NPC1L1 inhibitors, and discusses the current challenges.
Keywords: Cholesterol; Drug discovery; Hypercholesterolemia; Niemann-pick C1-Like 1.
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