Biochem/physiol Actions

LY2603618 (LCI-1) is a potent and selective checkpoint kinase 1 (Chk1) inhibitor (IC₅₀ = 7 nM) that produces a cellular phenotype identical to that reported upon Chk1 depletion by RNAi. LY2603618 prevents doxorubicin-induced Chk1 autophosphorylation (IC₅₀ = 52 nM; HeLa), allowing cells to traverse the G2/M checkpoint and proceed into mitosis with unresolved replicated chromosomes. LY2603618 renders mutant p53, but not wild-type, HT-29 colon cancer cells more sensitive to gemcitabine both in vitro and in mice in vivo.