source. BASILEA Non-Confidential Presentation 2022
Mitotic Checkpoint functions to monitor the eukaryotic cell eivision process to be divided without any error and this is controlled by binding and phosphorylation of diverse and complex proteins. BAL0891 inhibits two phosphorylating enzymes, threonine tyrosine kinase (TTK) and Polo-like kinase 1 (PLK1), which play key roles during the process.
Inhibiting TTK causes cells to split while spindle formation is incomplete which is called Mitotic override. In addition, inhibition of PLK1 induces Mitotic block, which fails to progress from metaphase to anaphase of cell division and is arrested at the G2/M phase. Both Mitotic override and mitotic block have mechanisms for interrupting the cancer cell-cycle which eventually leads cancer cells to apoptosis. Hence, anticancer drugs targeted for TTK and PLK1 ared actively being developed. Currently, CFI-402257(Treadwell)is in the clinical trial stage as a TTK inhibitor, and Onvansertib(Trovagene) is also in the clinical trial stage as a PLK1 inhibitor.
BAL0891 seems to be the only MCI that simultaneously inhibits both TTK and PLK1 so far. BAL0891 can strongly inhibit the growth of cancer because it can simultaneously inhibit two key phosphorylation enzymes. So far, there have been no cases of TTKinhibitors or PLK1 inhibitors approved as anticancer drugs. If BAL0891 is approved as a new drug, it can be the first anticancer drug in the MCI family and also the first-in-class anticancer drug which simultaneously inhibits both enzymes.