ArticleOncotarget2012
Computer-based identification of a novel LIMK1/2 inhibitor that synergizes with salirasib to destabilize the actin cytoskeleton.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Discovery and Development of a Potent LIMK2 Isoform-Specific Degrader.ACS chemical biology · 2026Article
- Regulation and signaling of the LIM domain kinases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.Journal of medicinal chemistry · 2022Article
- LIM Kinases, Promising but Reluctant Therapeutic Targets: Chemistry and Preclinical Validation In Vivo.Cells · 2022Review
- Article
- Pten and Dicer1 loss in the mouse uterus causes poorly differentiated endometrial adenocarcinoma.Oncogene · 2020Article
- Suppression of LIM Kinase 1 and LIM Kinase 2 Limits Glioblastoma Invasion.Cancer research · 2020Article
- Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy.Medicinal research reviews · 2019Review
- Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease.Nature genetics · 2018Article
- Quercetin Has Antimetastatic Effects on Gastric Cancer Cells via the Interruption of uPA/uPAR Function by Modulating NF-κb, PKC-δ, ERK1/2, and AMPKα.Integrative cancer therapies · 2018Article
- VEGF Triggers the Activation of Cofilin and the Arp2/3 Complex within the Growth Cone.International journal of molecular sciences · 2018Article
- Involvement of LIMK1/2 in actin assembly during mouse embryo development.Cell cycle (Georgetown, Tex.) · 2018Article
- Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1.Journal of virology · 2017Article
- LIM kinases: cofilin and beyond.Oncotarget · 2017Review
- LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation.Oncotarget · 2015Article
- Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.BMC microbiology · 2015Article
- Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway.Oncotarget · 2015Article
- Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.Journal of medicinal chemistry · 2015Article
- Nitric oxide enhances keratinocyte cell migration by regulating Rho GTPase via cGMP-PKG signalling.PloS one · 2015Article
- Molecular pathways: targeting the kinase effectors of RHO-family GTPases.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurofibromin regulates cell motility via three distinct GTPase pathways acting through two different domains, the Ras GTPase-activating protein-related domain (GRD) and the pre-GRD domain. First, the GRD domain inhibits Ras-dependent changes in cell motility through the mitogen activated protein cascade. Second, it also regulates Rho-dependent (Ras-independent) changes by activating LIM kinase 2 (LIMK2), an enzyme that phosphorylates and inactivates cofilin (an actin-depolymerizing factor). Third, the pre-GRD domain acts through the Rac1 GTPase, that activate the P21 activated kinase 1 (PAK1)-LIMK1-cofilin pathway. We employed molecular modeling to identify a novel inhibitor of LIMK1/2. The active sites of an ephrin-A receptor (EphA3) and LIMK2 showed marked similarity (60%). On testing a known inhibitor of EphA3, we found that it fits to the LIMK1/2-ATP binding site and to the latter's substrate-binding pockets. We identified a similar compound, T56-LIMKi, and found that it inhibits LIMK1/2 kinase activities. It blocked the phosphorylation of cofilin which led to actin severance and inhibition of tumor cell migration, tumor cell growth, and anchorage-independent colony formation in soft agar. Because modulation of LIMK by neurofibromin is not affected by the Ras inhibitor Salirasib, we examined the combined effect of Salirasib and T56-LIMKi each of which can affect cell motility by a distinct pathway. We found that their combined action on cell proliferation and stress-fiber formation in neurofibromin-deficient cells was synergistic. We suggest that this drug combination may be developed for treatment of neurofibromatosis and cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.