Anti-Mitotic Cancer Therapeutics

Background

Unregulated cell proliferation and evasion of cell death (apoptosis) are two of the fundamental hallmarks of cancer.  While a number of pharmacological agents can target cell proliferation or apoptosis, anti-mitotic agents have proven to be amoung the most clinically effective anti-cancer drugs.  The exceptional tumour inhibitory activity of anti-mitotics drugs is due to their unique ability to link perturbation of cell proliferation (metaphase arrest) with apoptosis (mitotic death and/or catastrophe) Figure 1.pdf

Data

In light of the clinical sucess of the anti-mitotic microtubule drug Taxol, the identification of new and improved anti-mitotic pharmacophores remains one of the primary objectives of current oncology drug discovery.  Indeed, in addition to improved microtubule drugs (Ixabepilone), inhibitors of Polo/Aurora kinases (BI-2536/VX-680) and mitotic kinesins (Ispinesib, GSK-923295) have recently emerged as highly promising new anti-cancer therapeutics.

Our Technology

BioPharmica has identified new anti-mitotic agents that induce mitotic arrest and apoptosis.  While these activities do not affect the microtubule cytoskeleton in interphase cells, they perturb the function of the mitotic spindle Figure 2.pdf, thereby selectively linking cell division with cell death.

In addition to defining the molecular and cellular modes of action of these compounds, BioPharmica is also actively pursuing hit optimization through in silico and in vitro medicinal chemistry.