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Inhibiting E3 ligases

Separate groups of researchers have identified highly selective small molecule inhibitors of E3 ubiquitin ligase,1,2 a large multi-subunit complex involved in protein degradation that has been considered difficult, if not impossible, to target. The compounds could represent a new class of cancer therapeutics that are more specific for malignant cells than previous drugs directed toward the proteasome.

The E3 ubiquitin ligase complex is a key component of the ubiquitin-proteasome system, the cell's chief mechanism of breaking down proteins. Dysfunction of the pathway occurs in a variety of cancers, including lymphomas and prostate, bladder and breast cancer.3,4

There is one marketed drug that targets the proteasome-Velcade bortezomib-and there are no disclosed compounds in the clinic against

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