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Updated: Aug 6, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Drugging p53 mutants: Recent advances using small-molecule modulation strategies
Elizabeth A Lopes1, Tomás G Monteiro2, Maria M M Santos2
1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa, 1649-003, Portugal; CBIOS - Research Center for Biosciences & Health Technologies, Universidade Lusófona - Centro Universitário de Lisboa, Campo Grande 376, Lisboa, 1749-024, Portugal.
European Journal of Medicinal Chemistry
|July 17, 2026
Summary
Researchers are developing small molecules to restore the tumor-suppressive function of mutant TP53 (p53) protein, a common event in cancer. This review covers recent advances in targeting mutated p53 for cancer therapy.
Area of Science:
- Oncology
- Medicinal Chemistry
- Molecular Biology
Background:
- TP53 is the most frequently mutated gene in human cancers.
- Mutations in TP53 lead to loss of p53 tumor-suppressive functions, promoting tumor progression, metastasis, and therapy resistance.
Purpose of the Study:
- To provide a comprehensive overview of recent advances in small-molecule modulators targeting mutant TP53 (mut p53).
- To focus on diverse mechanisms for mut p53 reactivation and discuss therapeutic potential.
Main Methods:
- Literature review of small-molecule mut p53 modulators reported between 2020 and 2025.
- Categorization of modulators based on their mechanisms of action (covalent electrophiles, metal-based coordinators, non-covalent modulators, chemical inducers of proximity).
Main Results:
- Significant progress in developing small molecules to restore p53 tumor suppressor activity.
- Highlighting key clinical candidates and emerging compounds with different modulation mechanisms.
- Discussion of mechanisms of action and therapeutic potential of these compounds.
Conclusions:
- Small-molecule modulators offer promising therapeutic strategies for restoring p53's tumor-suppressor function in cancer.
- Continued research and development in this area hold potential for novel cancer treatments.
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