HS56 is an ATP-competitive dual Pim/DAPK3 inhibitor with K i values of 0.26, 0.208, 2.94, and >100 μM for DAPK3, Pim-3, Pim-1, and Pim-2, respectively. HS56 inhibits LC20 phosphorylation and smooth muscle contraction. HS56 decreases blood pressure in spontaneously hypertensive mice. HS56 can be used in research of hypertension.