Apremilast

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Description

Apremilast (CC-10004) is an oral phosphodiesterase 4 inhibitor. The Ki-value (affinity constant) of apremilast for PDE4 is 68 nM. Apremilast binds to the catalytic site of the PDE4 enzyme, thereby blocking cAMP degradation. Apremilast (CC-10004) inhibits the production of TNF-α (IC50 = 0.11 μ), IFN-γ (IC50 = 0.013μ), and IL-12p70 (IC50 = 0.12 μ), as well as the chemokines CXCL9 (MIG), CXCL10 (IP-10), and CCL4 (MIP1a) from human peripheral blood mononuclear cells. In addition, apremilast inhibited N-formyl-Met-Leu-Phe-induced CD18 and CD11b expression leading to impaired adhesion of polymorphonuclear cells (PMN) to human umbilical vein endothelial cells. Apremilast blocks the synthesis of several pro-inflammatory cytokines and chemokines, such as tumor necrosis factor alpha, interleukin 23, CXCL9, and CXCL10 in multiple cell types. Apremilast also interferes with the production of leukotriene B4, inducible nitric oxide synthase, and matrix metalloproteinase and reduces complex inflammatory processes, such as dendritic cell infiltration, epidermal skin thickening, and joint destruction. Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. Apremilast is currently in phase III trials.

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