Antitumor activity of the novel oral highly selective Wee1 inhibitor Debio 0123

Abstract:

Background: The Wee1 tyrosine kinase is activated upon DNA damage and regulates the G2-M cell cycle checkpoint. Inhibition of Wee1, in conjunction with additional genetic alterations and/or addition of a DNA damaging agent, results in mitotic catastrophe and apoptosis of cancer cells, offering an attractive approach to treating cancer. The aim of the present study was to characterize the pharmacological properties of the newly discovered, orally available, and highly selective Wee1 inhibitor Debio 0123. Methods: Profiling of Debio 0123 was performed on 465 selected kinases in a cell-free system. Effects of Debio 0123 on downstream signaling were analyzed by ELISA and western blot in HT29 (colorectal adenocarcinoma) and A427 (lung carcinoma) cell lines. The in vitro growth inhibition activity of Debio 0123 was defined in a broad number of human cancer cell lines after 72h using a proliferation monolayer …

Año de publicación:

2019

Keywords:

Fuente:

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