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This program centers on the discovery of small molecule inhibitors of PCSK9, a clinically validated target for hypercholesterolemia. This target remains very attractive to the pharmaceutical industry and, with the recent approval of PCSK9-targeting antibodies, some companies are directing or redirecting their efforts towards the development of small molecules capable of inhibiting this target, as small molecules offer several advantages over biologics. In collaboration with Dr. Nabil Seidah from the Institut de Recherche Clinique de Montréal (IRCM) and NuChem therapeutics, small molecule hits targeting the intracellular inhibition of PCSK9 were identified. The molecules were active in various cell-based assays in the micromolar range.