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Updated: Jul 19, 2025

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

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
PubMed
Abstract

Insights

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.
Keywords:
Y220Capoptosisartificial intelligencemutant p53small molecule inhibitors

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