There is a strong need for new antimitotic drugs that overcome the limitations of the currently
used antitubulin compounds, mainly neurotoxicity and the development of resistance. One of the most
promising new targets is kinesin spindle protein (KSP, also known as Eg5), which contributes to the formation
of mitotic spindle during cell division and has not been reported to play any other cellular role so far.
This review covers KSP inhibitors binding at the allosteric, induced-fit L5 site reported between 2008 and December
2013. Among them, main groups include dihydropyrimidines, STLC derivatives, quinazoline-based compounds and pyrrole/
pyrazole and related agents. Structure-activity relationships are described, as well as the synthesis of representative
compounds. They are remarkably selective for KSP and produce G2/M mitotic arrest accompanied by a characteristic
monoastral cellular phenotype. Some of them have entered clinical trials, the most advanced being in Phase II. Therefore,
KSP inhibitors show great potential as future clinical antimitotic agents, especially due to their activity in taxane-resistant
Keywords: Antimitotic, Antitumor, Inhibitors, Kinesin spindle protein, Structure-activity relationships, Synthesis.
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