KSP/Eg5 Inhibition in Parasites and Fungi

The Kinesin Spindle Protein (KSP; a.k.a. Eg5 or KIF11) is a plus end-directed Kinesin-5 (a.k.a. BimC) subfamily member and has been the focus of significant drug development efforts for decades.  Currently, KSP (or its homologs) is a target for anti-mitotics (cancer)^1,2, anti-parasitics (malaria)³, and anti-fungals⁴. As a microtubule (MT) cross-linking enzyme, KSP plays a critical role in mitotic spindle pole separation, and its inhibition results in the formation of monoaster spindles which is thought to lead to mitotic catastrophe and apoptosis (Fig. 1). The targeting of KSP as a treatment for cancer is well-documented^1,2,5,6. The purpose of this newsletter is to briefly discuss KSP homologs as a therapeutic target for parasitic and fungal diseases...

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