Cell lines

U937 human monocytic cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Reaction Conditions

18h; IC50=74 nM

Applications

Apremilast was initially screened for PDE4 inhibition using a partially purified enzyme preparation from U937 human monocytic cells and which has been shown previously to contain predominantly PDE4B and PDE4D activities. Apremilast was also found to exhibit an IC50 of around 74 nM using 1 mM cAMP as substrate.

Animal models

SCID mice

Dosage form

5 mg·kg-1·day-1 ; oral taken

Applications

The pharmacological activity of apremilast (5 mg·kg-1·day-1 total divided into 2 daily doses) was tested in comparison with cyclosporine (5 mg·kg-1·day-1 total divided into 2 daily doses) and vehicle control (0.1 mL·day-1 divided into twice daily doses) in a mouse xenograft model of psoriasis. Epidermal thickness and proliferation index correlated with histological findings and demonstrated significant differences between treatment groups. Notably, apremilast caused statistically significant reductions in epidermal thickness (P< 0.001) and proliferation index (P< 0.001).

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Apremilast, also known as CC-10004, is a novel and potent small-molecule inhibitor of phosphodiesterase 4 (PDE4), a key enzyme involved in cyclic adenosine monophosphate (cAMP) degradation and cytokine production of inflammatory cells. Apremilast binds to the catalytic site of PDE4, with values of inhibition constant IC₅₀and affinity constantK_iof 0.074 μM and 68 nM respectively, consequently leading to the degradation of cAMP. Apremilast exhibits anti-inflammatory activities against inflammatory disease in animal models as well as human chronic inflammatory diseases (such as psoriasis and psoriatic arthritis) by blocking the synthesis of a range of pro-flammatory cytokines and chemokines, including tumor necrosis factor alpha, interleukin 23, CXCL9 and CXCL10.

Reference

[1].Georg Schett, Victor S. Sloan, Randall M. Stevens and Peter Schafer. Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and inflammatory disease. Ther Adv Musculoskelet Dis. 2010; 2(5): 271-278