Target intelligence / Profile preview

Kinesin-like protein KIF11 (KIF11) (KIF11)

Target
KIF11
Molecular classification
Enzyme, Motor protein, Kinesin
01

Overview

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].

Other names
Eg5Kinesin-5Kinesin spindle proteinKSPTRIP5KNSL1HKSPBimC
02

Mechanism of action

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.

03

Biological functions

MitosisSpindle assemblyCentrosome separationIntracellular transportCell proliferationMicrotubule-based movement
04

Disease associations

CancerMicrocephalyLymphedemaRetinopathyFamilial exudative vitreoretinopathy
05

Safety considerations

NeutropeniaMucositisPotential cognitive impairmentEmbryonic lethalityStomatitis
06

Interacting drugs

Ispinesib

6 more in the full profile.

07

Biomarkers

Mitotic indexPhospho-histone H3 (pH3)Monopolar spindle formationKIF11 mRNA/protein expression levels

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