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Verdine has since built a few different peptides that target disease pathways. The latest example could be a boon for cancer biology. It targets a protein called beta-catenin that is important for embryonic growth and development but can cause cancer–most commonly, colon cancer–when its production goes unchecked. Using the stapling approach, Verdine and his colleagues have developed a peptide that can move through cell membranes and directly target beta-catenin production at the DNA level. Tests in cell culture have been promising, and the group is about to begin animal studies.

“While it’s been known for many years that beta-catenin is a major player in several human cancers, it’s been impossible to attack it using traditional chemistry approaches,” says Frank McCormick, a cancer biologist and director of the Helen Diller Family Comprehensive Cancer Center at the University of California at San Francisco. “It’s on the list of proteins that the whole field would like to develop targets against but that, so far, have proven undruggable. It’s potentially a really big step forward.”

The second target Verdine and his colleagues attacked, interleukin 13, has been linked to the development of asthma. The resulting stapled peptide, three years in the making and still in early development, could help treat the underlying cause of disease with a drug that, due to its stapled formation, could be stable without refrigeration.

Verdine cofounded Aileron Therapeutics in 2005 to commercialize the stapled-peptide technology, and the company has since tested its peptides in multiple animal models of cancer. According to Verdine, Aileron plans to start its first human trials sometime next year.

“It’s a very attractive approach,” says McCormick. “The next step will be seeing if these drugs will make it all the way through to the clinic. We’ll be watching closely and with optimism.”

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Credit: Verdine Laboratory, Harvard University

Tagged: Biomedicine, cancer, drugs, protein, molecules, therapeutics

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