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Updated: Aug 6, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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
PubMed

Insights

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.
Keywords:
Chemical inducers of proximityChemical reactivation strategiesMutant p53 reactivationMutation-specific small moleculesS(N)Ar-based electrophiles

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