Related Experiment Video
Updated: Jan 21, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promising Activity in Hepatocellular Carcinoma
Sara Gomes1, Bartolomeo Bosco2, Joana B Loureiro1
1LAQV/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Cancers
|August 14, 2019
Summary
A new compound, SLMP53-2, reactivates mutant p53 (mutp53) and shows potent anticancer effects, particularly in hepatocellular carcinoma (HCC) models. This discovery offers a promising therapeutic strategy for cancers with TP53 mutations.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- TP53 mutations are prevalent in human cancers, inactivating the p53 tumor suppressor.
- Reactivating mutant p53 (mutp53) is a key therapeutic strategy for these cancers.
Purpose of the Study:
- To identify and evaluate novel mutp53 reactivators with anticancer potential.
- To investigate the mechanism of action and therapeutic efficacy of a lead compound, SLMP53-2.
Main Methods:
- Synthesis of a library of tryptophanol-derived oxazoloisoindolinones.
- Screening for anti-proliferative effects in p53-null cancer cells expressing mutp53.
- In vitro and in vivo studies in hepatocellular carcinoma (HCC) models.
Main Results:
- SLMP53-2 was identified as a potent mutp53 reactivator, restoring wild-type-like function and p53 transcriptional activity.
- SLMP53-2 induced cell cycle arrest, apoptosis, and endoplasmic reticulum stress in HCC cells.
- SLMP53-2 demonstrated synergistic effects with sorafenib and potent antitumor activity in HCC xenograft models with a favorable safety profile.
Conclusions:
- SLMP53-2 is a novel mutp53-targeting agent with significant therapeutic potential against HCC.
- Restoring p53 function via SLMP53-2 represents a promising strategy for treating TP53-mutated cancers.
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