The first-in-class alkylating HDAC inhibitor EDO-S101 is highly synergistic with proteasome inhibition against multiple myeloma through activation of multiple pathways.

This synergy was observed already at a 4 μ M drug concentration of EDO-S101 and yielded highly significant combination indices for both bortezomib and carfilzomib in a variety of MM cell lines, cell lines from hematologic (mantle cell lymphoma, ABC-type and GC-type diffuse large B-cell lymphoma, acute myeloid leukemia) and non-hematologic malignancies, as well as primary cells from hematologic cancers ( Supplementary Figures S4–S6 ; Supplementary Table S2 ).

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