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Mutant p53 targeting by the low molecular weight compound STIMA‐1
Abstract
Reactivation of mutant p53 in human tumor cells should induce cell death by apoptosis and thus eliminate the tumor. Several small molecules that reactivate mutant p53 have been identified. Here we show that STIMA‐1, a low molecular weight compound with some structural similarities to the previously identified molecule CP‐31398, can stimulate mutant p53 DNA binding in vitro and induce expression of p53 target proteins and trigger apoptosis in mutant p53‐expressing human tumor cells. Human diploid fibroblasts are significantly more resistant to STIMA‐1 than mutant or wild type p53‐carrying tumor cells. STIMA‐1 may provide new insights into possible mechanisms of mutant p53 reactivation and thus facilitate the development of novel anticancer drugs that target mutant p53‐carrying tumors.
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“Molecular docking structures revealed that STIMA-1,458 MIRA-1459–461 stictic acid424 and UCI-LC0023462 could bind in the L1/S3 pocket of p53-DBD, probably to the thiol group of Cys124 in this transiently opened pocket.424”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [458]
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Self-citationASPP Proteins Specifically Stimulate the Apoptotic Function of p53
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Self-citationCP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death
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Cited by
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
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Targeting mutant p53 for efficient cancer therapy
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Self-citationPRIMA-1 reactivates mutant p53 by covalent binding to the core domain
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Self-citationTherapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517
Metadata
- Authors
- Zache, N., Lambert, J. M. R., Rökaeus, N., Shen, J., Hainaut, P., Bergman, J., Wiman, K. G., & Bykov, V. J. N.
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2008-03-07
- Volume
- 2
- Issue
- 1
- Pages
- 70-80
- ISSN
- 1574-7891
- 1878-0261
- Cited by
- 96
- References
- 5
- Language
- en
- Update notices
- correction (2017-05-02)
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- Zache, N., Lambert, J. M. R., Rökaeus, N., Shen, J., Hainaut, P., Bergman, J., Wiman, K. G., & Bykov, V. J. N. (2008). Mutant p53 targeting by the low molecular weight compound STIMA‐1. Molecular Oncology. https://doi.org/10.1016/j.molonc.2008.02.004
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