(E/Z)-Zotiraciclib has a highly novel kinase inhibitory spectrum inhibiting 17 kinases from a panel of 63, 11 of which are CDK/JAK/FLT family members. The others, Lck, Fyn, Fms, TYRO3, ERK5, and p38δ, are implicated in inflammatory and proliferative processes. Human CYP1A2, 3A4, 2C9, and 2C19 isoforms are not inhibited by (E/Z)-Zotiraciclib at the highest tested concentration of 25 μM, but (E/Z)-Zotiraciclib inhibits CYP2D6 with IC50=0.95 μM, approximately at the plasma Cmax observed at the maximum tolerated dose. (E/Z)-Zotiraciclib inhibits cell proliferation concentrations in HCT-116 (IC50=0.079 μM) and HL-60 (IC50=0.059 μM). (E/Z)-Zotiraciclib is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. (E/Z)-Zotiraciclib is mainly metabolized by CYP3A4 and CY1A2 in vitro. (E/Z)-Zotiraciclib does not inhibit any of the major human CYPs in vitro except CYP2D6 (IC50=1 μM). (E/Z)-Zotiraciclib does not significantly induce CYP1A and CYP3A4 in human hepatocytes in vitro.