Kinesin-like protein KIF11 (Eg5) (Eg5)

Kinesin-like protein KIF11, widely referred to as Eg5, is a member of the kinesin-5 family of motor proteins and plays a critical role in the early stages of mitosis (UniProt P14136). It is responsible for the assembly and maintenance of the bipolar mitotic spindle by cross-linking and sliding anti-parallel microtubules, which drives centrosome separation (PubMed: 10521345). In the absence of functional Eg5, cells fail to form a bipolar spindle and instead develop a characteristic monoastral spindle, leading to cell cycle arrest in the M-phase and subsequent apoptosis. Because Eg5 is highly expressed in proliferating cells and various human cancers, it is a significant target for anti-cancer drug development (PubMed: 25411105). LY2523355 (Litronesib) is a potent, allosteric inhibitor of Eg5 that has been investigated in clinical trials for its ability to induce mitotic catastrophe in tumor cells (PubChem CID 49867587). While Eg5 inhibitors avoid the neurotoxicity often associated with microtubule-stabilizing agents like taxanes, their clinical utility has been limited by dose-limiting hematological toxicities, particularly neutropenia (PubMed: 25411105).

Other names

KIF11Kinesin family member 11KNSL1TRIP5HKSPKinesin-5En kinesin-like protein

Allosteric inhibition of the ATPase activity of the Eg5 motor domain, which prevents the transition to a microtubule-binding state, thereby inhibiting centrosome separation and inducing mitotic arrest.