UNASSIGNED: Targeting mitotic regulation is recognized as an important strategy for @entity5 therapy. @entity875 /B kinase and polo-like kinase 1 ( @entity9370 ) are the key mitotic regulators, and many inhibitors have been developed. Combinations of these inhibitors are anticipated to be more effective therapeutics compared with single-inhibitor treatments; however, a systematic analysis of the combined effects is lacking. Here, we constructed the first @entity1 cell mitotic regulation network model, which spans from mitotic entry to anaphase initiation, and contains all key mitotic kinase targets. The combined effects of different kinase inhibitors and microtubule inhibitors were systematically explored. Simultaneous inhibition of @entity16511 and @entity9370 strongly induces @entity5700 . Microtubule inhibitor dosage can be significantly reduced when combined with a @entity9370 inhibitor. The efficacy of these inhibitor combinations was validated by our experimental results. The mitotic regulatory network model provides a platform to study the complex interactions during mitosis, enables identification of mitotic regulators, and determines targets for drug discovery research. The suggested use of combining microtubule inhibitors with @entity9370 inhibitors is anticipated to enhance microtubule-inhibitor tolerance in a wide range of @entity1 .

Modeling the mitotic regulatory network identifies highly efficient anti- XXXX drug combinations.

@entity1 :: ('9606', 'Species') :: ['mammalian', 'patients'] @entity5700 :: ('MESH:D011123', 'Disease') :: ['polyploidy'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity875 :: ('6790', 'Gene') :: ['Aurora A'] @entity9370 :: ('5347', 'Gene') :: ['PLK1'] @entity16511 :: ('9212', 'Gene') :: ['Aurora B']
@entity5 :: (MESH:D009369,Disease) :: ['cancer']
