The development of the highly selective CDK9 inhibitor AZD-4573 (Table 2) was based on another selective, oral inhibitor of the amidopyridine series—AZ-5576, which was reasonably potent against the AML cell line MV-4-11, both ex and in vivo, but exhibited lower solubility in PBS and rate of metabolism in human microsomes, limiting its ability to provide a high therapeutic dose and optimal duration of target engagement within the clinical scenario. The gene discussed is CDK9; the disease is acute myeloid leukemia.