Inhibits Wee1 tyrosine kinase (IC50 = 5.2 nM) thus preventing phosphorylation of CDC2 and abrogating the G2 DNA damage checkpoint, sensitizing a variety of tumor cells to DNA damaging agents.1 Adavosertib also blocks Wee1 phosphorylation of E3 ubiquitin ligase SKP2 in human cells, ultimately preventing degradation of CDKs and further allowing cell cycle progression.2 Stimulates anti-tumor immunity and enhances sensitivity to immune checkpoint blockade by activating ERV and the dsRNA pathway.3 Potentiates sensitivity of tumors to PARP inhibitors.4
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