Chromobox2 inhibition: a novel activity of alisertib, an aurora A kinase inhibitor.

ABSTRACT: Chromobox 2 (CBX2), a subunit of Polycomb Repressor Complex 1 (PRC1), is expressed in high-grade serous carcinoma. CBX2 inhibitory peptide (CBX2i) has demonstrated efficacy in a syngeneic mouse model, but has limitations. We sought to identify an alternative approach to CBX2 inhibition. A computational-based molecular docking screen was performed using the SelleckChem Bioactive library to identify inhibitors of CBX2. A similarity screen of top hits against the bound conformation of CBX2i pharmacophore model was performed in parallel. A series of in vitro validation studies evaluated the effect of alisertib on proliferation, a CBX2 target gene, and stemness. CBX2 knockdown cell lines and a syngeneic murine model were utilized to evaluate alisertib response in the context of CBX2 loss. Cell

SUBMITTER: Yamamoto TM 

PROVIDER: S-EPMC12866977 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature