chemistry
june 2015
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ASNjournals
Dana-Farber.org
11
Dana-Farber made a chemical adapter that attaches to a targeted drug molecule, allowing the drug to bring the cell's protein-elimination machinery directly to the cancer protein. In essence, the chemical adapter enables the drug to attract the protein-degrader in order to demolish cancer proteins. The team first tested their technology on leukemia cells, beginning with a drug that inhibits a protein called BRD4 that controls the expression of cancer growth genes. They also designed an adapter to bind to a protein-degrading enzyme, and attached it to the drug. When the leukemia cells were treated with the drug attached to the adapter, BRD4 was degraded in less than an hour. Researchers believe that because this technology so rapidly and complete degrades cancer proteins, it may prevent cancer cells from developing resistance to targeted therapies.
The adapter is exceptionally selective. When the researchers measured the levels of all proteins in the leukemia cells after treatment, they discovered only a few proteins out of more than 7,000 in the cell were degraded. Furthermore, the technology generates little noticeable side effects. The researchers tested the adapter in mice with an aggressive form of leukemia, finding a quick degradation of BRD4 and a strong anti-leukemia effect with few harmful effects. Looking to the future, Dana-Farber researchers want to expand the strategy for the treatment of other cancers.
sources
Science Daily