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Development of WEE1 inhibitors with selectivity against PLK1

WEE1, regulates the G2/M cell cycle checkpoint, via by phosphorylating of CDK1 (aka Cdc2) at Tyr15, which inhibits CDK1/cyclin B kinase activity. Inhibition of WEE1 overrides DNA damage-induced cell cycle arrest in cells with a malfunctioning G1 checkpoint, leading TP53 mutant cancer cells into mitotic catastrophe (Duda et al, 2016). This makes WEE1 an appealing target for amplifying the impact of chemotherapeutic DNA-damaging therapies. Despite the advancement of the potent WEE1 inhibitor AZD1775 (MK1775) into clinical trials, recent reports suggest unexpected antiproliferative effects, possibly linked to poor kinase selectivity and inhibition of polo-like kinase 1 (PLK1). At Concept Life Sciences , we are dedicated to identifying and developing a highly selective WEE1 tool compound, offering a valuable resource for precise biological research and gaining deeper insights into WEE1's role

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