Therapeutic Targeting of Protein Disulfide Isomerase PDIA1 in Multiple Myeloma

Patients with multiple myeloma refractory to standard treatments have short survival. High PDIA1 expression confers resistance to proteasome inhibitors and other stressors due to the gain in ER-function, while maintaining or increasing vulnerability to PDIA1 inhibition. In this study we report the identification and characterization of an orally bioavailable novel PDIA1 inhibitor CCF642-34 that is effective against multiple myeloma in pre-clinical models. Overall design: MM1.S cells were treated with 3µM of either CCF642 or CCF642-34 for 6 hours and gene expression analysis was performed by RNA sequencing.