Chk2 Inhibitor is an indoloazepine checkpoint kinase inhibitor that mediates apoptosis and cell cycle arrest. Checkpoint kinase 2 is activated upon DNA damage or genomic instability which eventually causes apoptosis. Mechanistic studies show that Chk2 inhibitor causes autophosphorylation of Chk2 at Thr68 and targets ATP binding pockets of Chk2. Further studies demonstrate that Chk2 inhibitors also inhibit Chk1 and MEK-1 and affect interleukin-2 (IL-2), TNF-α, MEK-1, and GSK-3β.
1. Sharma, V. and Tepe, J.J. 2004. Bioorg. Med. Chem. Lett. 14: 4319-4321. PMID: 15261294 2. Sharma, V., et al. 2004. J. Med. Chem. 47: 3700-3703. PMID: 15214798 3. Jobson, A.G., et al. 2009. J. Pharmacol. Exp. Ther. 331: 816-826. PMID: 19741151 4. Yeh, Y.H., et al. 2009. Oncogene. 28: 1366-1378. PMID: 19151762
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YehYeh, YH. et al. (PubMed 19151762) used the Chk2 Inhibitor to present a regulatory loop between TTK/hMps1 and Chk2 whereby DNA damage-activated Chk2 may facilitate the stabilization of TTK/hMps1, therefore maintaining the checkpoint control. -SCBT Publication Review
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