Description
Chk2 inhibitor II is a selective, ATP-competitive inhibitor of the DNA damage control kinase, checkpoint kinase 2 (IC
50 = 15 nM). It has been shown to prevent apoptosis in human T-cells exposed to ionizing radiation (EC
50 = 3-7.6 μM). This compound has been used to target the role of Chk2 in cellular signaling in response to DNA damage.
Uses
Chk2 Inhibitor II is a selective APT-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2).
Biochem/physiol Actions
Chk2 Inhibitor II is a checkpoint kinase 2 inhibitor, which controls the p53 response to DNA breaks induced by radiation, leading to apoptosis. Protection of T-cells from apoptosis implies use as an adjuvant for radiation therapy in cancer. IC50 = 15 nM; Ki = 37 nM. Chk2 Inhibitor II shows 1000-fold greater selectivity for the Chk2 serine/threonine kinase than for the Cdk1/B and CK1 kinases (for which IC50 = 12 μM and 17 μM, respectively). Chk2 Inhibitor II weakly inhibits a panel of 31 other kinases (<25% inhibition at a concentration of 10 μM and prevents apoptosis of human CD4+ and CD8+ T-cells subjected to ionizing radiation (EC50 = 3 μM and 7.6 μM, respectively).
References
1) Arienti et al. (2005), Checkpoint kinases inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles; J. Med. Chem., 48 1873
2) Pereg et al. (2006), Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage; Mol. Cell. Biol., 26 6819
