Definition

An inhibitor of threonine tyrosine kinase (TTK; monopolar spindle 1 kinase; Mps1) and polo-like kinase 1 (PLK1; PLK-1; STPK13), with potential mitotic checkpoint inhibiting (MCI) and antineoplastic activities. Upon administration, TTK/PLK1 inhibitor BAL0891 selectively targets, binds to and inhibits TTK and PLK1. This disrupts and inactivates the spindle assembly checkpoint (SAC), which results in chromosomal misalignment and missegregation, mitotic checkpoint complex destabilization, and induces G2/M-phase cell-cycle arrest, aberrant cell division and apoptosis in TTK- and PLK1-overexpressing tumor cells. PLK1, a serine/threonine kinase that is crucial for the activation of the mitotic SAC and regulation of mitosis, plays a key role in tumor cell proliferation, transformation and invasion. PLK1 expression is upregulated in a variety of tumor cell types and high expression is associated with increased aggressiveness and poor prognosis. TTK, a tyrosine and serine/threonine kinase expressed in proliferating normal tissues, is essential for proper SAC functioning, chromosome alignment and segregation. Overexpressed in various human tumors, TTK plays a key role in uncontrolled tumor cell growth.