CLPP inhibition with A2-32-01 shows synergy with other clinically and mechanistically relevant agents for myeloma. The autophagy inhibitor chloroquine enhances MM1.S and H929 myeloma cell death in combination with A2-32-01 (A), whereas combination index (CI) analysis shows moderate to strong synergy under most conditions examined (B). Similar results were noted when A2-32-01 was combined with the glycolysis and PPP inhibitor 6-aminonicatinamide (6-AN) (C-D). Finally, combinations of A2-32-01 with the PIs bortezomib (BTZ) (E) and carfilzomib (CFZ) (F) also showed enhanced activity, and synergy was confirmed by CI analysis for both (G-H).