Video Experimental Relacionado

Updated: Jul 20, 2026

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

CX-5461 y doxorrubicina activan una respuesta transcripcional compartida asociada con el daño del ADN en

Sayan Paul¹, José A Gutiérrez¹, Alyssa R Bogar¹

¹Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555, USA.

G3 (Bethesda, Md.)

|January 16, 2026

Abstract:

CX-5461 (CX) is under investigation for the treatment of late-stage cancers. While CX was first described as an RNA polymerase I inhibitor, it has recently been shown to primarily inhibit the beta isoform of topoisomerase II. This isoform is also inhibited by anthracycline drugs including Doxorubicin (DOX) and mediates the toxic effects of these drugs on the heart. It is unclear whether CX will similarly cause cardiotoxicity. We therefore tested the effects of CX on iPSC-derived cardiomyocytes from six individuals. CX induces cell death in cardiomyocytes at micromolar concentrations. Transcriptome profiling following treatment over time reveals gene expression programs that correspond to the DNA damage response, which are pathways shared with DOX response genes. Micromolar CX concentrations affect heart-specific genes and 14 functionally-validated genes in loci associated with DOX cardiotoxicity. Our data demonstrate the impact of CX on the transcriptome of cardiomyocytes, a potential off-target cell type of the drug.

Palabras clave:

CX-5461 doxorrubicina RNA-seq cardiotoxicidad enfermedad cardiovascular expresión génica global topoisomerasa II

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