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Nature Chemical Biology

June 21, 2010

A new 'stapled' peptide selectively inhibits MCL-1 ― a pro-survival protein ― thus sensitizing cancer cells to stimuli that induce apoptosis, programmed cell death. The results published online this week in Nature Chemical Biology provide an important new tool to inhibit MCL-1 in cells and may be the basis for the development of novel therapeutics for MCL-1 mediated cancers or chemotherapy-resistance.

Cancer cells frequently express high levels of anti-apoptotic proteins to promote their immortality. In particular, MCL-1 has emerged as an important therapeutic target because it has been linked to a number of cancers, as well as resistance to chemotherapies. Loren Walensky and colleagues report the identification, structural analysis and functional validation of the first cell-permeable and selective MCL-1 inhibitor. The authors further demonstrated that this stapled peptide sensitized a leukemia cell line to TRAIL, an activator of the apoptotic pathway in cells.

DOI:10.1038/nchembio.391 | Original article

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