XL844 + gemcitabine

XL844 + gemcitabine is an experimental combination therapy consisting of **XL844**, a selective small molecule inhibitor of checkpoint kinases **Chk1 and Chk2**, and **gemcitabine**, a nucleoside analog used as chemotherapy. XL844 competitively inhibits Chk1 at the ATP-binding site and potently inhibits Chk2, leading to abrogation of DNA damage checkpoints (notably the G2 and S phase checkpoints), impairment of DNA repair, and promotion of mitotic catastrophe and apoptosis in tumor cells. Preclinical models demonstrated that XL844 substantially enhances the cytotoxicity of gemcitabine in various cancer cell lines and xenograft models, with evidence for augmented DNA damage and antitumor activity. This combination had entered phase I clinical trials for advanced malignancies including lymphoma and chronic lymphocytic leukemia but the development was terminated at phase 1 due to slow recruitment and/or other development factors[1][2][3][4][5][6][8].