Kinesin family motor proteins (KIFs) (KIFs)

Kinesin family motor proteins (KIFs) constitute a large superfamily of ATP-dependent molecular motors that move unidirectionally along microtubule tracks to transport various cellular cargoes, including vesicles, organelles, and protein complexes [1.3.2, 1.3.5]. In humans, the superfamily consists of 45 members divided into 14-15 families, which are essential for fundamental processes such as intracellular trafficking, axonal transport in neurons, and the orchestration of mitosis and meiosis [1.1.3, 1.4.2]. During cell division, mitotic kinesins like KIF11 (Eg5) and CENP-E (KIF10) are critical for spindle assembly, pole separation, and accurate chromosome segregation [1.4.1, 1.4.4]. Due to their pivotal role in cell proliferation, several kinesins are frequently overexpressed in various cancers and have become significant therapeutic targets [1.2.2, 1.4.5]. Small-molecule inhibitors targeting the ATPase activity or allosteric sites of mitotic kinesins have been developed to induce mitotic arrest and apoptosis in tumor cells [1.1.1, 1.4.4]. Unlike traditional microtubule-targeting agents such as taxanes, kinesin inhibitors specifically target the motor proteins rather than the microtubules themselves, potentially offering a more selective therapeutic approach with a reduced risk of peripheral neurotoxicity [1.4.1]. Clinical development has primarily focused on KIF11 and CENP-E inhibitors, though challenges such as dose-limiting neutropenia remain a concern [1.4.2, 1.4.5].

Other names

Kinesin superfamily proteinsKIFsMolecular motorsMicrotubule-based motor proteinsKinesin-like proteins

Inhibition of ATPase activity, allosteric inhibition of the motor domain, disruption of microtubule binding, induction of mitotic arrest (monoastral spindles), and promotion of apoptosis [1.1.1, 1.4.4].