LY2606368 is a checkpoint kinase 1 (Chk1) inhibitor with a Ki value of 0.9 nM against the purified target and IC50 values of <13 nM in a viability study of multiple colorectal cancer cell lines. Inhibition of Chk1 causes double-strand DNA breakage in cells leading to an excessive cell damage burden and subsequent cell death. In vitro, LY2606368 inhibits the doxorubicin-activated G2/M checkpoint in p53-deficient HeLa cells with an EC50 value of 9 nM. LY2606368, at 25 nM, also significantly induces apoptosis and inhibits colony formation in AGS and MKN1 gastric cancer cells.
LY 2606368 is a novel CHK1 inhibitor under investigation as a chemopotentiating agent. It causes double-stranded DNA breakage while simultaneously removing the protection of the DNA damage checkpoints. LY 2606368 is representative of a novel class of drugs for the treatment of cancer and tumor growth inhibition.
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