Apremilast-d5 (Synonyms: APR-d5)

Apremilast-d₅ is intended for use as an internal standard for the quantification of apremilast by GC- or LC-MS. 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 the 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 the clinical score in mouse models of arthritis.⁴

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 inhibitorJournal of Medicinal Chemistry52(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 psoriasisBritish Journal of Pharmacology159(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 diseaseJ.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 arthritisArthritis Research & Therapy12(3)(2010)