AZD5438 a potent cyclin-dependent kinase (cdk) 1, 2 and 9 inhibitor with IC50 of 16, 6 and 20 nM, respectively. AZD5438 exhibits antiproliferative activity in human tumor cell lines. AZD5438 blocks cell cycling at G2-M, S and G1 phases. AZD5438 reduces the proportion of actively cycling cells in vivo. In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC50 range, 0.2-1.7 ��M), causing inhibition of the phosphorylation of cdk substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain and blocking cell cycling at G2-M, S, and G1 phases. In vivo, when orally administered at either 50 mg/kg twice daily or 75 mg/kg once daily, AZD5438 inhibited human tumor xenograft growth. In vivo, AZD5438 reduced the proportion of actively cycling cells.
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