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Comparison of the lactone 21b to the corresponding acid 21c in enzymatic and cellular assays. (A) Hydrolysis of the lactone ring to generate the ring-opened acid 21c with improved HMGCR inhibition. (B) and (C) HepG2 cells treated with 21b or 21c at indicated doses for 16 h, were analyzed for protein levels. The data are represented as %HMGCR remaining relative to the DMSO-control (defined as 100%), and presented as the mean ± SD from two repeated experiments shown in Fig. S4.
