prexasertib-ly2606368

Description: Prexasertib (also known as LY2606368) is a novel, potent, selective and ATP competitive inhibitor of the CHK1 (checkpoint kinase 1) protein kinase with IC50 values of< 1 nM and 8 nM for CHK1 and CHK2, respectively. CHK1 is a multifunctional protein kinase integral to both the cellular response to DNA damage and control of the number of active replication forks. CHK1 inhibitors are currently under investigation as chemopotentiating agents due to CHK1's role in establishing DNA damage checkpoints in the cell cycle. Prexasertib as a single agent causes double-stranded DNA breakage while simultaneously removing the protection of the DNA damage checkpoints. The action of Prexasertib is dependent upon inhibition of CHK1 and the corresponding increase in CDC25A activation of CDK2, which increases the number of replication forks while reducing their stability. Treatment of cells with Prexasertib results in the rapid appearance of TUNEL and pH2AX-positive double-stranded DNA breaks in the S-phase cell population. Prexasertib shows similar activity in xenograft tumor models, which results in significant tumor growth inhibition. In summary, Prexasertib is a potent representative of a novel class of drugs for the treatment of cancer that acts through replication catastrophe.

References: Mol Cancer Ther. 2015 Sep; 14(9):2004-13; Am J Cancer Res. 2017 Mar 1; 7(3):473-483.

Related CAS: 1234015-55-4 (mesylate); 1234015-52-1 (free base); 1234015-57-6 (mesylate hydrate) 1234015-54-3 (2HCl) 2100300-72-7 (lactate hydrate)