molecules of the month

“I was told early on that developing an oral PCSK9 inhibitor is impossible.” The Merck macrocyclic PCSK9 protein-protein interaction (PPI) inhibitor, MK-0616, is a once-daily PCSK9-lowering and LDL-cholesterol-lowering small molecule that has recently demonstrated antibody-like efficacy as an oral agent in the clinic. The program highlights numerous technical achievements at the forefront of modern drug discovery, from mRNA display screening to the use of lipidic permeation enhancer formulations, and will set a standard for modern “classics in drug discovery” for some time. As the first author of the Ph. II trial report, Dr. Christie Ballantyne summarizes, “I was told early on that developing an oral PCSK9 inhibitor is impossible. But the technology keeps advancing. It’s very exciting to see the…