KIF11 inhibitors(National Research Centre in Egypt)

Acute myeloid leukaemia (AML) is a heterogeneous haematological malignancy. Despite advances in therapy, its prognosis remains poor with limited improvement in survival. KIF11 (Eg5), a kinesin motor protein essential for spindle dynamics during mitosis, interacts with microtubules. Inhibition of KIF11 disrupts spindle poles, impairs chromosome segregation, and induces mitotic arrest and apoptosis, making it a potential therapeutic target. SB-743921, a selective KIF11 inhibitor, has shown potent anti-tumour activity in various cancers. It effectively inhibits AML cell proliferation, induces cell cycle arrest, and suppresses tumour progression. In vitro, it exhibits potent cytotoxic activity against various AML cell lines, and KIF11 knockdown further confirms its pivotal role in AML. RNA sequencing reveals that SB-743921 downregulates key pathways (e.g. MYC, E2F and G2M). In vivo, SB-743921 delays tumour growth and prolongs survival in AML mice with minimal toxicity, thus supporting its clinical potential. These findings support further investigation on clinical applications and clinical strategies for addressing of this challenging disease.