Yale: Current drugs block the actions of only about a quarter of known disease-causing proteins, but Yale University researchers have developed a technology capable of not just inhibiting, but destroying every protein it targets. The new type of drug, called Proteolysis Targeting Chimeras (PROTACs), also can continue to destroy mutant proteins in mouse tumors, according to a new study published June 10 in the journal Nature Chemical Biology.
“This new drug modality
culminates a decade of work in the field by my lab,” said Craig Crews,
the Lewis B. Cullman Professor of Molecular, Cellular, and Developmental
Biology and senior author of the paper, which was done in collaboration
with scientists from GlaxoSmithKline and Arvinas, LLC.
current drugs are small molecules designed to fit into the folds of
disease-causing proteins and inhibit their function. High doses are
often needed to ensure that protein function is blocked sufficiently to
produce therapeutic results, which in turn can produce harmful side
In contrast, PROTACs engage the cells’ own protein
degradation machinery to destroy targeted proteins by tagging them for
removal and can do so multiple times, meaning it can work at lower
doses, the authors say. This suggests this new type of drug has not only
the potential to target proteins that are not currently
“pharmaceutically vulnerable” but could do so safely, Crews said.
“This is a game-changer for drug development,” Crews said.
PROTAC technology is being commercialized by New Haven biotechnology
company Arvinas, LLC, which recently signed a $434 million partnership
from pharmaceutical giant Merck to further explore the potential of the
Crews is scientific founder of Arvinas, LLC and
Proteolix, Inc., which developed the next generation multiple myeloma
drug Kyprolis® based on work from his lab. The study was funded by the National Institutes of Health and GlaxoSmithKline.