CCF642 is a novel PDI-inhibiting compound with antimyeloma activity.The IC50 is 2.9 μmol/L.In vitro: CCF642 inhibit PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. CCF642 causes acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release.In vivo: CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. CCF642 can be given intravenously without injection reactions in mice with 10 mg/kg.
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