AZD5438 is an orally-bioavailable imidazole-pyrimidine inhibitor of cyclin dependent kinase (CDK) 1, 2, and 9 at IC50s of 16, 6, and 20 nM, respectively. In vitro AZD5438 showed significant antiproliferative activity in human tumor cell lines with IC50s in the range of 0.2-1.7 uM, inhibiting phosphorylation of CDK substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II carboxylate-terminus. AZD5438 blocks cell cycling at the G2-M, S, and G1 phases and maintains suppression of biomarkers such as phospho-pRbSer249/Thr252 for up to 16h following a single oral dose in SW620 cells. [1]