ArticleCancer research2018
Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- MRCKα represses GEF-H1 mediated RhoA activation to promote ovarian cancer spheroid growth and invasion.bioRxiv : the preprint server for biology · 2026Article
- Autoimmunity-associated DIORA1 binds the MRCK family of serine/threonine kinases and controls cell motility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Non-muscle myosin II-dependent cumulus cell migration at ovulation is required for sperm to reach the egg in mice.Communications biology · 2025Article
- An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells.Nature communications · 2024Article
- Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry.International journal of molecular sciences · 2024Article
- MRCK as a Potential Target for Claudin-Low Subtype of Breast Cancer.International journal of biological sciences · 2024Article
- MRCK activates mouse oocyte myosin II for spindle rotation and male pronucleus centration.The Journal of cell biology · 2023Article
- Review
- RHO GTPase family in hepatocellular carcinoma.Experimental hematology & oncology · 2022Review
- MRCK: a master regulator of tissue remodeling or another 'ROCK' in the epithelial block?Tissue barriers · 2021Review
- Progress in the therapeutic inhibition of Cdc42 signalling.Biochemical Society transactions · 2021Review
- Article
- Article
- Targeting the cytoskeleton against metastatic dissemination.Cancer metastasis reviews · 2021Review
- Article
- Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation.Journal of biomedical science · 2021Article
- The CDC42 effector protein MRCKβ autophosphorylates on Threonine 1108.Small GTPases · 2020Article
- Epidermal ROCK2 induces AKT1/GSK3β/β-catenin, NFκB and dermal tenascin C; but enhanced differentiation and p53/p21 inhibit papilloma.Carcinogenesis · 2020Article
- Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products.Natural product reports · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 4 institutions in 1 country.
Funding
Abstract
The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here, we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphologic changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent antiproliferative effects with greatest activity in hematologic cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy.
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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.