^
    7d
    Computational validation of inhibitors for human phosphatidylinositol 4-phosphate 5-kinase-type 1 α protein implicated in cancer. (PubMed, J Biomol Struct Dyn)
    Four protein kinase inhibitors, R547, GDC-0879, JNJ-7706621 and ABT-869 were found to bind hPIP5K1α via a stable complex formation. The hit molecules display favorable ADME properties and are predicted to be non-carcinogenic. The hit molecules in particular R547, have better binding free energies compared to reference molecule, ISA-2011B.
    Journal
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    PIP5K1A (Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha)
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    GDC 0879 • linifanib (ABT-869) • R-547
    over3years
    A novel cell-based assay for the high-throughput screening of epithelial-mesenchymal transition inhibitors: Identification of approved and investigational drugs that inhibit epithelial-mesenchymal transition. (PubMed, Lung Cancer)
    We systematically screened approved, investigational, and druggable compounds with inhibitory effects using a reporter assay, and identified candidate drugs for EMT inhibition.
    Journal
    |
    CDH1 (Cadherin 1) • VIM (Vimentin) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    CDH1 expression • VIM expression
    |
    GDC 0879
    over4years
    MEK1/2 is a bottleneck that induces cancer stem cells to activate the PI3K/AKT pathway. (PubMed, Biochem Biophys Res Commun)
    The miPS cells were cultured for one week in the presence of the conditioned medium (CM) of Lewis lung carcinoma (LLC) cells and AZD-6244, PD0325901, a pan-MEK inhibitor, or GDC-0879, a B-Raf inhibitor. Moreover, converted cells gained migration and invasion abilities assessed by in vitro assays. Therefore, the inhibition of MEK1/2 was found to be critical for the conversion of normal stem cells into CSCs in the tumor-inducing microenvironment.
    Journal
    |
    BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CD44 (CD44 Molecule) • CD24 (CD24 Molecule)
    |
    CD44 expression
    |
    Koselugo (selumetinib) • Gomekli (mirdametinib) • GDC 0879