ArticleOncotarget2015
LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Integrating multi-omics data revealing LIMK1 as a metastatic biomarker in LUAD patients with brain metastasis.Cancer cell international · 2026Article
- LIMK2 inactivation suppresses mechanical stimulation-induced dermal fibroblast differentiation and resistance to apoptosis.Scientific reports · 2026Article
- Rational design and structural Bioinformatics-Driven discovery of tetrapeptide inhibitors for LIMK-Targeted cancer therapy.Medical oncology (Northwood, London, England) · 2025Article
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.Cell biochemistry and biophysics · 2025Article
- Are You a Friend or an Enemy? The Dual Action of Methylglyoxal on Brain Microvascular Endothelial Cells.International journal of molecular sciences · 2025Article
- Rottlerin inhibits macropinocytosis of Porcine Reproductive and Respiratory Syndrome Virus through the PKCδ-Cofilin signaling pathway.PloS one · 2025Article
- Exosomal mRNA Signatures as Predictive Biomarkers for Risk and Age of Onset in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- LIM kinases in cardiovascular health and disease.Frontiers in physiology · 2024Review
- LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.Cells · 2023Review
- Role of protein phosphorylation in cell signaling, disease, and the intervention therapy.MedComm · 2022Review
- The phosphorylation level of Cofilin-1 is related to the pathological subtypes of gastric cancer.Medicine · 2022Article
- LIM Kinases, Promising but Reluctant Therapeutic Targets: Chemistry and Preclinical Validation In Vivo.Cells · 2022Review
- Article
- Protein domain-based prediction of drug/compound-target interactions and experimental validation on LIM kinases.PLoS computational biology · 2021Article
- Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo.Journal of cellular and molecular medicine · 2021Article
- Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis.Cancers · 2021Review
- Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis.Frontiers in cell and developmental biology · 2021Review
- Upregulated Transcription Factor PITX1 Predicts Poor Prognosis in Kidney Renal Clear Cell Carcinoma-Based Bioinformatic Analysis and Experimental Verification.Disease markers · 2021Article
- Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy.
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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.