ArticleNature chemical biology2009
Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages.
Article in Nature chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 257 citations in OpenAlex.
- DUSP1 is a key driver of disease persistence and potential therapeutic target in hairy cell leukemia.Blood advances · 2026Article
- Zebrafish swimming towards cures: a scalable NAM platform for drug discovery.Drug discovery today · 2026Review
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- DUSP6 inhibitor (E/Z)-BCI hydrochloride stimulates glucose clearance and adipose lipolysis in diet-induced obese mice.Genes & diseases · 2026Article
- Role of dual specificity phosphatase 1 in influencing inflammatory pathways in macrophages modulated byFrontiers in immunology · 2026Article
- Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells.Stem cell reports · 2025Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase.Nature communications · 2025Article
- Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated bybioRxiv : the preprint server for biology · 2025Article
- Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity.Science (New York, N.Y.) · 2025Article
- Zebrafish as a Versatile Model for Cardiovascular Research: Peering into the Heart of the Matter.Cells · 2025Review
- Restraint of inflammasome-driven cytokine responses through the mRNA stability protein TTP.Cell reports · 2025Article
- The vertebrate segmentation clock drives segmentation by stabilizing Dusp phosphatases in zebrafish.Developmental cell · 2025Article
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis.Development (Cambridge, England) · 2024Article
- In Vivo Chemical Screening in Zebrafish Embryos Identified FDA-Approved Drugs That Induce Differentiation of Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2024Article
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression.Scientific reports · 2024Article
- Calcium-Dependent Regulation of Neuronal Excitability Is Rescued in Fragile X Syndrome by a Tat-Conjugated N-Terminal Fragment of FMRP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.Purinergic signalling · 2024Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The dual-specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth factor (FGF) signaling to limit the activity of extracellular signal-regulated kinases (ERKs) 1 and 2. We have identified a small-molecule inhibitor of Dusp6-(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI)-using a transgenic zebrafish chemical screen. BCI treatment blocked Dusp6 activity and enhanced FGF target gene expression in zebrafish embryos. Docking simulations predicted an allosteric binding site for BCI within the phosphatase domain. In vitro studies supported a model in which BCI inhibits Dusp6 catalytic activation by ERK2 substrate binding. We used BCI treatment at varying developmental stages to uncover a temporal role for Dusp6 in restricting cardiac progenitors and controlling heart organ size. This study highlights the power of in vivo zebrafish chemical screens to identify new compounds targeting Dusp6, a component of the FGF signaling pathway that has eluded traditional high-throughput in vitro screens.
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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.