Related Experiment Video
Updated: Jul 19, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
9.6K
AI-powered discovery of a novel p53-Y220C reactivator
Shan Zhou1, Dafei Chai1, Xu Wang1
1Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United States.
Frontiers in Oncology
|August 18, 2023
Summary
Artificial intelligence identified compound H3, which restores wild-type p53 conformation in the p53-Y220C mutation. This compound selectively kills cancer cells and inhibits tumor growth in mice.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The p53-Y220C mutation is a frequent driver of cancer progression.
- Restoring wild-type p53 function is a therapeutic strategy for cancers with this mutation.
Purpose of the Study:
- To identify small-molecule compounds that restore wild-type p53 conformation in the p53-Y220C mutant.
- To evaluate the efficacy of identified compounds in preclinical cancer models.
Main Methods:
- Artificial intelligence (AI)-powered virtual screening of 10 million compounds.
- Experimental validation using cell lines with various p53 mutations.
- In vivo efficacy assessment in a mouse xenograft model.
Main Results:
- AI identified 83 high-scoring compounds, with H3 showing preferential activity against p53-Y220C mutant cells.
- Compound H3 restored wild-type p53 conformation and transcriptional activity.
- H3 induced cell cycle arrest, apoptosis, and reduced tumor growth in mice.
Conclusions:
- AI facilitated the discovery of H3, a selective p53-Y220C reactivator.
- H3 demonstrates therapeutic potential for inhibiting tumor development in p53-Y220C-driven cancers.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
4.6K
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...
4.6K
02:04Covalently Linked Protein Regulators
6.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.9K
02:53Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K