Table 1.

Main biological effects of IMiDs

Molecular effect	Mechanism of action
1. Inhibition of angiogenesis9–12	Inhibition of secretion of VEGF and bFGF inhibition of cytokine-stimulated endothelial cell migration and cell adhesion.
2. Direct induction of apoptosis13	Induction of apoptosis or G1 growth arrest in MM cell lines and in patient MM cells that are resistant to melphalan, doxorubicin, and dexamethasone. Enhancement of the anti-MM activity of dexamethasone.
3. Indirect induction of apoptosis14–17	Expansion of T-cells and natural killer cells and augmentation of their function. Enhancement of activity of caspase-8, increased sensitivity to Fas induction, inhibition of the expression of the cellular inhibitor of apoptosis protein-2, and potentiation of other apoptosis inducers, such as TNF-related apoptosis-inducing ligand.
4. CRBN depletion18,19	Downregulation of TNF-α and T-cell immunomodulatory activity.

Abbreviations: bFGF, basic fibroblast growth factor; CRBN, cereblon; IMiDs, immunomodulatory drugs; MM, multiple myeloma; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.