Apremilast

Apremilast is an inhibitor of phosphodiesterase 4 (PDE4) with an IC₅₀ value of 74 nM when tested in U937 cell lysates with 1 mM cAMP.^1,2 It is orally active, significantly decreasing epidermal thickness and epithelial cell proliferation index in a mouse model of psoriasis.² Apremilast reduces both TNF-α and matrix metalloproteinase-3 production in gut lamina propria mononuclear cells from patients with inflammatory bowel disease.³ It also blocks spontaneous production of TNF-α from human rheumatoid synovial cells and improves clinical score in mouse models of arthritis.⁴

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1. Man, H.W., Schafer, P., Wong, L.M., et al. Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. J. Med. Chem. 52(6), 1522-1524 (2009).

2. Schafer, P.H., Parton, A., Gandhi, A.K., et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br. J. Pharmacol. 159(4), 842-855 (2010).

3. Gordon, J.C., Prothero, J.D., Thornton, C.A., et al. CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-α and MMP-3 production in patients with inflammatory bowel disease. J. Crohns Colitis 3(3), 175-182 (2009).

4. McCann, F.E., Palfreeman, A.C., Andrews, M., et al. Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res. Ther. 12(3), (2010).