Background: Cholesterol, derived from two different sources of endogenous synthesis and diet, is
essential for the growth and maintenance of mammalian cells. However, elevated level of serum
cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce
endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption
inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann-
Pick C1-like 1 (NPC1L1).
Objective: The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of
NPC1L1 and discovery of novel chemical entities by virtual screening.
Conclusion: Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in
azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone
also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose
novel cholesterol absorption inhibitors.