Paper on a new compound revealing a non-catalytic function of AURORA-A kinase published09/30/2020
Elmar Wolf, PI in a MSNZ Joint Project, has published a paper on a new compound, which degrades AURORA-A kinase, a protein involved in cancer development.
The mitotic kinase AURORA-A is essential for cell cycle progression and is considered a priority cancer target. Although the catalytic activity of AURORA-A is essential for its mitotic function, recent reports indicate an additional non-catalytic function, which is difficult to target by conventional small molecules.
Elmar Wolf, Bikash Adhikari, and colleagues therefore developed a series of chemical degraders (PROTACs). One degrader induced rapid, durable and highly specific degradation of AURORA-A. Degrader-mediated AURORA-A depletion caused an S-phase defect, which is not the cell cycle effect observed upon kinase inhibition, supporting an important non-catalytic function of AURORA-A during DNA replication.
AURORA-A degradation induced rampant apoptosis in cancer cell lines and thus represents a versatile starting point for developing new therapeutics to counter AURORA-A function in cancer.
The abstract of the paper can be found here (Nature Chemical Biology).