A high blood cholesterol (LDL-c) level is a well-known risk factor for cardiovascular disease. The important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in cholesterol homeostasis has been confirmed by the gain- and loss-of-function PCSK9 variations in human populations and two recently FDA approved antibody drugs. However, these antibody drugs are expensive and require injection. Small molecule degraders of PCSK9 naturally emerge as an alternative promising strategy. We recently identified small molecule hits that can reduce the PCSK9 level in cell-based phenotypic screening. We will present the synthesis and our preliminary structure activity relationship studies of these indole-containing heterocycles.

Structure activity relationship studies of indole-containing heterocycles targeting lipid regulation pathways

255th National Meeting (2018)

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