Old cancer drugs with a modern mechanism

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Science  09 Jun 2017:
Vol. 356, Issue 6342, pp. 1041-1042
DOI: 10.1126/science.356.6342.1041-f

Some cancer drugs are rationally designed on the basis of their known interaction with specific target molecules that drive tumorigenesis. Others are mechanistically poorly understood but are developed because they display anticancer activity with low toxicity in preclinical models. Uehara et al. have identified the mechanism underlying the anticancer activity of a class of drugs in the latter category—the sulfonamides. They find that three different sulfonamides (E7820, indisulam, and CQS) induce formation of a complex between a specific RNA-splicing factor and a specific E3 ubiquitin ligase. This interaction promotes selective degradation of the splicing factor. Interestingly, selective protein degradation also explains the activity of an unrelated cancer drug called lenalidomide.

Nat. Chem. Biol. 10.1038/nchembio.2363 (2017).

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