ArticleProceedings of the National Academy of Sciences of the United States of America2022
Development of an improved inhibitor of Lats kinases to promote regeneration of mammalian organs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- EDNRB-dependent endothelin signaling reduces proliferation and promotes proneural-to-mesenchymal transition in gliomas.Molecular oncology · 2026Article
- Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.Molecular and cellular biochemistry · 2026Article
- A universal 6iL/E4 culture system for deriving and maintaining embryonic stem cells across mammalian species.Cell research · 2026Article
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- Positive TAZ-TDG feedback loop drives proneural-to-mesenchymal transition to promote glioblastoma progression.Journal of translational medicine · 2026Article
- LATS kinase activity and tumor suppressor function are regulated by a second autophosphorylation site.The Journal of biological chemistry · 2026Article
- Establishment of a coculture system for Porphyromonas gingivalis and head and neck squamous cell carcinoma using spheroid culture and LATS inhibition.FEBS open bio · 2026Article
- In vivo screen reveals specific roles of Hippo pathway components in development and regeneration.Life science alliance · 2026Article
- Mechano-matching hydrogel patch promotes myocardial infarction repair via YAP-Bcl-2 pathway activation.Materials today. Bio · 2026Article
- Transient proliferation by reversible YAP and mitogen control of the cyclin D1/p27 ratio.Communications biology · 2026Article
- Hippo-YAP/TAZ signaling in inner ear development, injury, and regeneration: evidence synthesis and the biomechanical brake hypothesis.Frontiers in cell and developmental biology · 2026Review
- Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD.bioRxiv : the preprint server for biology · 2025Article
- Liver regeneration: unraveling the molecular mechanisms and clinical application.Journal of translational medicine · 2025Review
- Piezo1-mediated mechanotransduction controls osteocyte maturation and dendrite development via a YAP-CCN-Src signaling axis.Nature communications · 2025Article
- Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025Review
- Lats1/2 Are Essential for Developmental Vascular Remodeling and Biomechanical Adaptation to Shear Stress.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Discovery and Optimization of LATS1 and LATS2 Kinase Inhibitors for Use in Regenerative Medicine.Journal of medicinal chemistry · 2025Article
- Epithelial-Mesenchymal Transition Activates YAP to Drive Malignant Progression and Immune Evasion.Cancers · 2025Article
- YAP1 promotes adipogenesis by regulating the negative feedback mechanism of the Hippo signaling pathway via LATS2.Zoological research · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
The Hippo signaling pathway acts as a brake on regeneration in many tissues. This cascade of kinases culminates in the phosphorylation of the transcriptional cofactors Yap and Taz, whose concentration in the nucleus consequently remains low. Various types of cellular signals can reduce phosphorylation, however, resulting in the accumulation of Yap and Taz in the nucleus and subsequently in mitosis. We earlier identified a small molecule, TRULI, that blocks the final kinases in the pathway, Lats1 and Lats2, and thus elicits proliferation of several cell types that are ordinarily postmitotic and aids regeneration in mammals. In the present study, we present the results of chemical modification of the original compound and demonstrate that a derivative, TDI-011536, is an effective blocker of Lats kinases in vitro at nanomolar concentrations. The compound fosters extensive proliferation in retinal organoids derived from human induced pluripotent stem cells. Intraperitoneal administration of the substance to mice suppresses Yap phosphorylation for several hours and induces transcriptional activation of Yap target genes in the heart, liver, and skin. Moreover, the compound initiates the proliferation of cardiomyocytes in adult mice following cardiac cryolesions. After further chemical refinement, related compounds might prove useful in protective and regenerative therapies.
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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.