^
    2years
    A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier. (PubMed, Biomedicines)
    KW-2478, buparlisib, and minocycline hydrochloride (MH) promoted maximal expression of the junctional protein β-catenin and induced 4T1 cells nucleus changes...MH was the most promising in preventing 4T1 migration and BBB disruption, tumour and endothelial cytoskeleton-associated proteins modifications, and miRNA deregulation. Our data revealed MH's ability to improve BBB properties, while compromising BCCs viability and interaction with BBB endothelial cells, besides restoring miRNAs' homeostasis, paving the way for MH repurposing for BCBM prevention.
    Journal
    |
    HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    buparlisib (AN2025) • KW 2478 • minocycline
    over2years
    The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification. (PubMed, Exp Hematol Oncol)
    This finding demonstrated that KW-2478 had anticancer properties in imatinib-sensitive and imatinib-resistant CML cells and illustrated the possible mechanisms. This study provides an alternative choice for CML treatment, especially for TKI-resistant patients with BCR/ABL amplification and TKI-intolerant patients.
    Journal
    |
    CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CCNB1 (Cyclin B1) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    imatinib • KW 2478
    over3years
    Anti-NSCLC activity in vitro of Hsp90 inhibitor KW-2478 and complex crystal structure determination of Hsp90-KW-2478. (PubMed, J Struct Biol)
    Among them, twenty-two derivatives exhibited increased binding force with Hsp90 evaluated by molecular docking assay. The results would provide new guidance for anti-NSCLC new drug development based on the lead compound KW-2478.
    Preclinical • Journal
    |
    HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    KW 2478
    4years
    Effect of the Hsp90 Inhibitor KW-2478 on HepG2 Cells. (PubMed, Anticancer Agents Med Chem)
    KW-2478 inhibited the proliferation of HepG2 cells, induced apoptosis and cell cycle arrest, inhibited invasion, and promoted senescence. KW-2478 affected the expression of related factors in the mitochondrial apoptotic signaling and cell cycle-related regulatory pathways. KW-2478 downregulated the expression of STAT3, which is a key factor in the JAK-STAT pathway, indicating that KW-2478 may affect the function of HepG2 cells by downregulating STAT3.
    Journal
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STAT3 expression
    |
    KW 2478