Comparisons of translation inhibitors PF8503 and PF846.

(A) Structures of PF-06446846 (PF846, left) and PF-06378503 (PF8503, right). (B) Effect of PF846 and PF8503 doses on extracellular levels of PCSK9 secreted by Huh7 cells after overnight incubation. Experiment carried out in 4 (PF846) or 3 (PF8503) biological replicates, with standard deviations shown for each compound concentration. (C) Proteins stalled by PF8503 or PF846 in Huh7 cells after 1 hr treatment, shown based on the log2(fold change) of reads relative to vehicle control. Reads were quantified 3’ of the DMax position, as described in the Materials and Methods. Experiment carried out in biological triplicate, with the average plotted. (D) PF8503 sensitive protein sequences in Huh7 cells. The sequences are aligned according to the last main pause site position. Putative locations of the nascent peptide chains in the ribosome exit tunnel and relative to the ribosomal P and A sites are marked. Also indicated are the codon positions of the stall site and DMax positions.