ArticleMolecular cancer therapeutics2016
Structure-Based Screen Identification of a Mammalian Ste20-like Kinase 4 (MST4) Inhibitor with Therapeutic Potential for Pituitary Tumors.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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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
16 citing papers in PubMed, 23 citations in OpenAlex.
- STK26 Promotes the Stabilization of ATF6 to Facilitate the Progression of Colorectal Cancer.International journal of molecular sciences · 2025Article
- The Pivotal Role of Irradiation-induced Autophagy Mechanisms in Glioma Therapy.Anti-cancer agents in medicinal chemistry · 2025Review
- USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5.Theranostics · 2025Article
- Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.OncoTargets and therapy · 2025Article
- The mammalian Sterile 20-like kinase 4 (MST4) signaling in tumor progression: Implications for therapy.Cancer letters · 2023Review
- AURKB Enhances Chromosomal Remodeling of Telomeric Genes and Accelerates Tumorigenesis of Uveal Melanoma.Investigative ophthalmology & visual science · 2023Article
- Article
- Hesperadin suppresses pancreatic cancer through ATF4/GADD45A axis at nanomolar concentrations.Oncogene · 2022Article
- Identification of a dual TAOK1 and MAP4K5 inhibitor using a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Downregulation of MST4 Underlies a Novel Inhibitory Role of MicroRNA Let-7a in the Progression of Retinoblastoma.Investigative ophthalmology & visual science · 2020Article
- MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice.Behavioural neurology · 2020Article
- Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.Oncotarget · 2018Article
- Regulation of cell proliferation and metastasis by microRNA-593-5p in human gastric cancer.OncoTargets and therapy · 2018Article
- MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma.Cancer cell · 2017Article
- MST4 kinase phosphorylates ACAP4 protein to orchestrate apical membrane remodeling during gastric acid secretion.The Journal of biological chemistry · 2017Article
- Fungal KATs/KDACs: A New Highway to Better Antifungal Drugs?PLoS pathogens · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pituitary tumors of the gonadotrope lineage are often large and invasive, resulting in hypopituitarism. No medical treatments are currently available. Using a combined genetic and genomic screen of individual human gonadotrope pituitary tumor samples, we recently identified the mammalian sterile-20 like kinase 4 (MST4) as a protumorigenic effector, driving increased pituitary cell proliferation and survival in response to a hypoxic microenvironment. To identify novel inhibitors of the MST4 kinase for potential future clinical use, computational-based virtual library screening was used to dock the SelleckChem kinase inhibitor library into the ATP-binding site of the MST4 crystal structure. Several inhibitor candidates were identified with the potential to bind with high affinity. Using a TR-FRET in vitro recombinant kinase assay, hesperadin, initially described as an Aurora kinase inhibitor, exhibited potent inhibition of the MST4 kinase at nanomolar concentrations. The LβT2 gonadotrope pituitary cell hypoxic model was used to test the ability of this inhibitor to antagonize MST4 actions. Under short-term severe hypoxia (1% O2), MST4 protection from hypoxia-induced apoptosis was abrogated in the presence of hesperadin. Similarly, under chronic hypoxia (5%), hesperadin blocked the proliferative and colony-forming actions of MST4 as well as the ability to activate specific downstream signaling and hypoxia-inducible factor-1 effectors. Together, these data identify hesperadin as the first potent, selective inhibitor of the MST4 kinase with the capacity to block pituitary tumor cell growth in a hypoxic microenvironment.
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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.