Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance

Eg5, the product of Kif11 gene, also known as kinesin spindle protein, is a motor protein involved in proper establishment bipolar mitotic spindle. Eg5 one 45 different kinesins coded human genome superfamily. Over last three decades has attracted great interest promising new target. The identification monastrol specific inhibitor ATPase activity domain inhibiting microtubule motility vitro and cellulo sparked an intense academia industry to pursue novel small molecules that target order be used cancer chemotherapy based on anti-mitotic strategy. Several inhibitors entered clinical trials. Currently field faced with problem most tested exhibited only limited efficacy. However, inhibitor, Arry-520 (clinical name filanesib), demonstrated efficacy patients multiple myeloma scheduled enter phase III At same time, trends research are emerging, including increased binding sites focus drug synergy established antitumor agents improve chemotherapeutic This review presents updated view structure function Eg5-inhibitor complexes, traces possible development resistance their potential therapeutic applications, surveys current challenges future directions this active discovery.