New manuscript: Synthesis and comparison of Bub1 inhibitors
Updated: Jul 20, 2020
Congratulation to Ilma Amalina, not only has she successfully defended her PhD thesis but her thesis work is now available on Biorxiv.
We have had a long standing interest in the Bub1, a serine/threonine kinase involved in both the spindle assembly checkpoint (SAC) and mitotic chromosome alignment. It is well documented that Bub1 phosphorylates Histone 2A at T120 (H2ApT120) which is required for recruitment of Sgo1 to centromeres.
Small-molecule inhibitors are invaluable tools for studying kinase function, so in this study Ilma compared to Bub1 inhibitors, namely of 2OH-BNPPI and BAY-320. Using some nice assays that we set up by a previous PhD student - Ailsa Bennett - Ilma confirmed that while both agents inhibit Bub1 in vitro, only BAY-320 effectively inhibits Bub1 in cells. However, the high concentrations required for cellular inhibition raises concerns about off-target effects highlighting the need for improved Bub1 inhibitors.