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Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site

Abstract:

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures...

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Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1016/j.ccell.2020.11.013

Authors


Publisher:
Cell Press Publisher's website
Journal:
Cancer Cell Journal website
Volume:
39
Issue:
2
Pages:
225-239
Publication date:
2020-12-24
Acceptance date:
2020-11-18
DOI:
EISSN:
1878-3686
ISSN:
1535-6108
Pmid:
33357454
Language:
English
Keywords:
Pubs id:
1151760
Local pid:
pubs:1151760
Deposit date:
2021-01-05

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