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Kinesin-like protein KIF11, commonly known as Eg5 or Kinesin Spindle Protein (KSP), is a plus-end-directed motor protein essential for the formation and maintenance of the bipolar mitotic spindle [1, 2]. It functions as a homotetramer that cross-links and slides antiparallel microtubules, providing the mechanical force necessary for centrosome separation and chromosome alignment during mitosis [5, 10]. KIF11 is frequently overexpressed in various malignancies, including breast, lung, and colorectal cancers, where it drives uncontrolled cell proliferation and is associated with poor prognosis [4, 15]. Pharmacological inhibition of the KIF11 motor domain leads to the characteristic formation of "monoaster" spindles, triggering the spindle assembly checkpoint and subsequent apoptotic cell death [1, 11]. While several KIF11 inhibitors have entered clinical trials as anti-cancer agents to avoid the neurotoxicity associated with taxanes, their efficacy as monotherapies has been limited [11, 13]. Beyond its role in cancer, germline mutations in KIF11 are linked to developmental disorders such as microcephaly-lymphedema-chorioretinopathy syndrome (MCLMR), highlighting its importance in brain and lymphatic development [7, 19].
Inhibition of the kinesin motor domain ATPase activity, which prevents centrosome separation and leads to the formation of characteristic monopolar spindles (monoasters), resulting in mitotic arrest at the G2/M phase and subsequent apoptosis.
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