LDHA/PDKs-IN-2 (compound 20k) is a potent and dual inhibitor of PDKs and LDHA with IC 50 s of 1.6 and 0.7 μM, respectively. LDHA/PDKs-IN-2 reduces A549 cell proliferation with an EC 50 of 15.7 μM and decreases the lactate formation, and increases oxygen consumption. LDHA/PDKs-IN-2 has the potential for the research of cancer diseases.