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    DRUG:

    OTS514

    i
    Other names: OTS514
    Company:
    OncoTherapy
    Drug class:
    TOPK inhibitor
    3ms
    PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites. (PubMed, Nat Commun)
    Eviction of Ikaros is rapidly reversed by addition of the PBK-inhibitor OTS514, revealing dynamic regulation by kinase and phosphatase activities...PBK-deficient cells were able to divide but showed altered chromatin accessibility and nucleosome positioning consistent with CTCF retention. Our studies reveal that PBK controls the dissociation of selected factors from condensing mitotic chromosomes and contributes to their compaction.
    Journal
    |
    IKZF1 (IKAROS Family Zinc Finger 1) • IKZF3 (IKAROS Family Zinc Finger 3)
    |
    OTS514
    over1year
    The oncogenic kinase TOPK upregulates in psoriatic keratinocytes and contributes to psoriasis progression by regulating neutrophils infiltration. (PubMed, Cell Commun Signal)
    This study identified a crucial role of TOPK in psoriasis by regulating neutrophils infiltration, providing new insights into the pathogenesis of psoriasis.
    Journal
    |
    CXCL8 (Chemokine (C-X-C motif) ligand 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IL17A (Interleukin 17A) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
    |
    OTS514
    over2years
    KRAS mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer. (PubMed, J Cell Mol Med)
    In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5-FU, and the combinatory use of OTS514 and KRAS inhibitor AMG510 showed synergistic anti-tumour effect. These results suggest that KRAS-TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PBK (PDZ Binding Kinase)
    |
    KRAS mutation
    |
    5-fluorouracil • Lumakras (sotorasib) • OTS514