BioCentury
ARTICLE | Product R&D

Stalling translation

How Pfizer’s translation-blocking small molecules inhibit tough targets

April 20, 2017 11:19 PM UTC

Pfizer Inc. has discovered a mechanism to create small molecule inhibitors of PCSK9 by halting translation of the protein as it emerges from the ribosome. While the company is remaining tight-lipped about that program, it believes the strategy will have important ramifications for other targets that have proven intractable for oral drug development.

Last month, Pfizer published a study in PLoS Biology describing the identification of PF-06446846, a small molecule that blocks translation of PCSK9 by binding the ribosomal complex and blocking its exit tunnel...