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Isogranulatimide is a cell-permeable alkaloid containing indole/maleimide/imidazole skeleton that acts as a potent, reversible and ATP-competitive inhibitor of Chk1 (IC50 = 100 nM) and GSK-3β (IC50 = 500 nM). Isogranulatimide inhibits G2 DNA damage checkpoint-associated kinases, Chk2, Cdk1, and DNA-PK only at much higher concentrations (IC50 = 3 µM, 10 µM, and 10 µM, respectively). Isogranulatimide only minimally affects the activities of a panel of 11 other kinases tested (IC50 ≥ 40 µM). When used in combination with γ-irradiation, it is also reported to selectively arrest the growth of MCF-7 cells lacking p53 function.
Jiang, X., et al. 2004. Mol. Cancer Ther. 3, 1221. Roberge, M., et al. 1998. Cancer Res. 58, 5701.
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