Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors

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Updated: Jul 9, 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

Natalia Issaeva1, Przemyslaw Bozko, Martin Enge

  • 1Microbiology and Tumor Biology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Nature Medicine
|November 24, 2004
PubMed

Insights

A novel compound, RITA (reactivation of p53 and induction of tumor cell apoptosis), reactivates the tumor-suppressor p53 protein. This drug candidate shows promise for treating cancers with wild-type p53 by inducing tumor cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Wild-type p53's tumor-suppressor function is often lost in cancer due to HDM-2 mediated degradation.
  • HDM-2 negatively regulates p53 by targeting it for proteasomal degradation, a common mechanism in tumors retaining wild-type p53.

Purpose of the Study:

  • To identify novel small molecules that can restore p53 tumor-suppressor activity.
  • To evaluate the therapeutic potential of RITA (reactivation of p53 and induction of tumor cell apoptosis) as an anticancer agent.

Main Methods:

  • Chemical library screening to identify p53-binding compounds.
  • In vitro and in vivo assays to assess RITA's effect on p53-HDM-2 interaction and p53 target gene expression.
  • Evaluation of RITA's efficacy in various tumor cell lines and in vivo tumor models.

Main Results:

  • RITA binds to p53, inducing its accumulation and preventing its interaction with HDM-2 and other negative regulators.
  • RITA activates p53 target genes, leading to massive apoptosis in wild-type p53 tumor cells.
  • RITA demonstrates p53-dependent antitumor effects in vivo and suppresses tumor growth.

Conclusions:

  • RITA effectively reactivates wild-type p53's tumor-suppressor function.
  • RITA shows potential as a lead compound for developing novel anticancer drugs targeting tumors with intact p53 pathways.

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