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Article

Zinc Metallochaperones Reactivate Mutant p53 Using an ON/OFF Switch Mechanism: A New Paradigm in Cancer Therapeutics

18 Jun 2018

Abstract excerpt

Abstract Purpose: Zinc metallochaperones (ZMC) are a new class of anticancer drugs that reactivate zinc-deficient mutant p53 by raising and buffering intracellular zinc levels sufficiently to restore zinc binding. In vitro pharmacodynamics of ZMCs indicate that p53-mutant activity is ON by 4–6 hours and is OFF by 24. We sought to understand the mechanism of this regulation and to translate these findings...

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PMID: 29914895
DOI: 10.1158/1078-0432.ccr-18-0822

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