Figure 1.

Schematic diagram of the NF-κB signaling pathway and anti-multiple myeloma (MM) drug targets. First-line anti-MM drugs (highlighted in orange) passively target the canonical and/or non-canonical pathways to shut down NF-κB signaling. For example, bortezomib inhibits the 26S proteasome to hinder the processing of p105 and p100 proteins, to prevent gene transcription activation in canonical and non-canonical NF-κB signaling pathways, respectively; dexamethasone induces IκB protein synthesis to inhibit p105 processing; lenalidomide reduces RelA binding to open chromatin; cyclophosphamide is a DNA alkylating agent that disrupts DNA replication and genome stability. Ligands, adaptor proteins and transcriptional complexes involved in canonical NF-κB signaling are depicted in dark blue, whereas those involved in non-canonical NF-κB signaling are depicted in light blue; kinases are depicted in green; inhibitors are depicted in red. P and Ub indicate the post-translational modifications of phosphorylation and ubiquitination, respectively. Arrows with triangle heads indicate activation, whereas arrows with rhomboid heads indicate inactivation/inhibition; direct interactions are indicated by solid lines, whereas indirect interactions are indicated by dash lines.