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Biological Activity
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Description
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LY2603618 (IC-83) is a selective Chk1 inhibitor with potential anti-tumor activity. |
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Targets
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Chk1 |
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IC50 |
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In Vitro
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Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, LY2603618 prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving LY2603618 has not been published until now. [1] Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. [2] LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells. [3] |
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In Vivo
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In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. [3] |
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Clinical Trials
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A Phase I study of to assess the effect of LY2603618 on the metabolic pathway of Desipramine is ongoing. |
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Features
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References |
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[1] Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
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[2] Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.
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[3] Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.
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