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AZD8421 is a selective CDK2 inhibitor (IC50: 9 nM) with selectivity for CDK1, CDK4 and CDK6. AZD8421 inhibits cancer cell proliferation by inhibiting pRB phosphorylation, inducing cell cycle arrest and senescence. AZD8421 demonstrated promising single efficacy and synergy with CDK4/6 inhibitors such as Palbociclib (HY-50767) in in vivo breast and ovarian models. AZD8421 also has potent single-agent inhibitory activity against drug-resistant breast cancer cells.

[1] Denz C R, et al. Targeting the cell cycle with AZD8421, a potent and highly selective CDK2 inhibitor[J]. Cancer Research, 2024, 84(6_Supplement): 5730-5730.