Related Experiment Video

Updated: Jun 12, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Pharmacological reactivation of mutant p53: from protein structure to the cancer patient

K G Wiman1

  • 1Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden. klas.wiman@ki.se

Oncogene
|May 26, 2010
PubMed

Insights

Restoring function to mutant p53 protein, a common cancer driver, offers a promising new therapeutic strategy. Compounds like PRIMA-1 and APR-246 reactivate mutant p53, inducing cancer cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • The p53 tumor suppressor pathway is crucial for preventing cancer by inducing apoptosis or senescence.
  • Mutations in p53 are prevalent in human cancers, impairing its tumor-suppressive functions.
  • Restoring wild-type p53 activity in tumors is a viable therapeutic strategy.

Purpose of the Study:

  • To explore pharmacological reactivation of mutant p53 as a novel cancer therapy.
  • To identify and characterize small molecules that can restore p53 function.

Main Methods:

  • Screening of chemical libraries and rational drug design were employed.
  • The compound PhiKan083 was identified, binding to the Y220C p53 mutation.
  • PRIMA-1 was found to restore wild-type p53 conformation and induce apoptosis.

Main Results:

  • PhiKan083 stabilizes mutant p53 by binding to a specific mutation site.
  • PRIMA-1 restores wild-type p53 conformation, leading to apoptosis in tumor cells.
  • The PRIMA-1 analog APR-246 is undergoing clinical trials.

Conclusions:

  • Pharmacological reactivation of mutant p53 is a promising anticancer strategy.
  • Small molecules targeting mutant p53 hold potential for significant impact in cancer treatment.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

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

Published on: August 4, 2019

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...