ArticleArchives of toxicology2018
Stem cells are the most sensitive screening tool to identify toxicity of GATA4-targeted novel small-molecule compounds.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Age-dependent mitochondrial toxicity in renal stem cells: A precise 3D silk matrix model.Genes & diseases · 2026Article
- GATA4-targeted compounds induce apoptosis and diminish viability of hepatoblastoma cells.PloS one · 2026Article
- Antibiotic approaches to endodontic regeneration.Biomaterial investigations in dentistry · 2026Review
- Melanocortin 1 Receptor Regulates Pathological and Physiological Cardiac Remodeling.Journal of the American Heart Association · 2025Article
- Affinity chromatography reveals direct binding of the GATA4-NKX2-5 interaction inhibitor (3i-1000) with GATA4.Scientific reports · 2024Article
- α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor.EMBO reports · 2024Article
- Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound.Stem cell research & therapy · 2024Article
- Development of Advanced Oral-on-a-Chip: Replicating the Intricate Human Oral Microenvironment.International journal of biological sciences · 2024Article
- Review
- Transcriptomics reveal stretched human pluripotent stem cell-derived cardiomyocytes as an advantageous hypertrophy model.Journal of molecular and cellular cardiology plus · 2022Article
- Application of Human Induced Pluripotent Stem Cell Technology for Cardiovascular Regenerative Pharmacology.Methods in molecular biology (Clifton, N.J.) · 2022Article
- High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni.Analytical and bioanalytical chemistry · 2021Article
- GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line.Stem cell research & therapy · 2021Article
- GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes.Archives of toxicology · 2020Article
- Fabrication and Characterization of Drug-Loaded Conductive Poly(glycerol sebacate)/Nanoparticle-Based Composite Patch for Myocardial Infarction Applications.ACS applied materials & interfaces · 2020Article
- Targeting GATA4 for cardiac repair.IUBMB life · 2020Review
- Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in pharmacology · 2020Article
- Synthesis, Identification, and Structure-Activity Relationship Analysis of GATA4 and NKX2-5 Protein-Protein Interaction Modulators.Journal of medicinal chemistry · 2019Article
- Highlight report: Cell type selection for toxicity testing.EXCLI journal · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Safety assessment of drug candidates in numerous in vitro and experimental animal models is expensive, time consuming and animal intensive. More thorough toxicity profiling already in the early drug discovery projects using human cell models, which more closely resemble the physiological cell types, would help to decrease drug development costs. In this study we aimed to compare different cardiac and stem cell models for in vitro toxicity testing and to elucidate structure-toxicity relationships of novel compounds targeting the cardiac transcription factor GATA4. By screening the effects of eight compounds at concentrations ranging from 10 nM up to 30 µM on the viability of eight different cell types, we identified significant cell type- and structure-dependent toxicity profiles. We further characterized two compounds in more detail using high-content analysis. The results highlight the importance of cell type selection for toxicity screening and indicate that stem cells represent the most sensitive screening model, which can detect toxicity that may otherwise remain unnoticed. Furthermore, our structure-toxicity analysis reveals a characteristic dihedral angle in the GATA4-targeted compounds that causes stem cell toxicity and thus helps to direct further drug development efforts towards non-toxic derivatives.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.