The steroidal natural product cortistatin A, which has quinoline moiety as a hinge component and steroidal core responsible for extensive intermolecular forces with the ATP-binding cavity, showed a highly potent ATP-competitive CDK8 inhibitory activity (IC50 = 15 nM) that exhibited anticancer activity in animal models of acute myeloid leukemia (AML) (Cee et al., 2009; Crown, 2017; Pelish et al., 2015; Rzymski et al., 2017). Senexin B with 4-aminoquinazoline scaffold showed potent CDK8 modulation with an IC50 value of 24 nM (McDermott et al., 2017; Rzymski et al., 2015). Here, CDK8 is linked to acute myeloid leukemia.