ArticleThe Journal of biological chemistry2015
Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 74 citations in OpenAlex.
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- A feasibility of computational drug screening for Fuchs endothelial corneal dystrophy.Scientific reports · 2025Article
- Future protein alternative: recent progress and challenges in cellular agriculture.Food science and biotechnology · 2025Review
- Mesenchymal stromal cell chondrogenesis under ALK1/2/3-specific BMP inhibition: a revision of the prohypertrophic signalling network concept.Stem cell research & therapy · 2024Article
- In Vitro Modelling of Osteogenesis Imperfecta with Patient-Derived Induced Mesenchymal Stem Cells.International journal of molecular sciences · 2024Article
- Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation.Aging cell · 2023Article
- Epiprofin Transcriptional Activation Promotes Ameloblast Induction From Mouse Induced Pluripotent Stem CellsFrontiers in bioengineering and biotechnology · 2022Article
- Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors.Cancers · 2021Article
- RGMa can induce skeletal muscle cell hyperplasia via association with neogenin signalling pathway.In vitro cellular & developmental biology. Animal · 2021Article
- Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice.Frontiers in cell and developmental biology · 2021Article
- A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids.Cellular and molecular bioengineering · 2020Article
- Review
- Bu-M-P-ing Iron: How BMP Signaling Regulates Muscle Growth and Regeneration.Journal of developmental biology · 2020Review
- Structural biology of the TGFβ family.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Elevated BMP and Mechanical Signaling Through YAP1/RhoA Poises FOP Mesenchymal Progenitors for Osteogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways.Nature communications · 2019Article
- Pharmacologic Strategies for Assaying BMP Signaling Function.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Depletion of MOB1A/B causes intestinal epithelial degeneration by suppressing Wnt activity and activating BMP/TGF-β signaling.Cell death & disease · 2018Article
- Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells.eLife · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
GDF8, or myostatin, is a member of the TGF-β superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescued myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis.
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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.