A cell-permeable, pyrimidine derivative that acts as an ATP-competitive CDK Inhibitor (Ki=2.5uM for CDK1, and Ki=1.3uM for CDK2), and demonstrates cytostatic properties among a panel of 57 cancer cell lines. Also inhibits ATR kinase (IC50=6.7uM in MCF7 cells), but does not interfere with irradiation-induced autophosphorylation of DNA-PK or ATM. Potentiates a range of DNA-damaging cytotoxic drugs such as hydroxyurea (1.8-fold) and cisplatin (1.4-fold) at 10uM, but not the anti-mitotic paclitaxel. Attenuates G2/M arrest following DNA damage and inhibits RAD51 focus formation. Shown to be synthetically lethal when DNA single-strand break repair is impaired in PARP-inhibited cells.
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