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.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 62 mg/mL|
A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults.
Samrao A, et al. Arch Dermatol. 2012 Aug;148(8):890-7. PMID: 22508772.
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.
Man HW, et al. J Med Chem. 2009 Mar 26;52(6):1522-4. PMID: 19256507.
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