ロタミラスト

E6005 is an inhibitor of phosphodiesterase 4 (PDE4; IC₅₀ = 2.8 nM). It is selective for PDE4 over PDE1, PDE2, PDE3, and PDE5 with only 46.1, 51.6, 69.4, and 57.4% inhibition, respectively, at 30 μM. It inhibits the production of various cytokines in isolated human lymphocytes and monocytes (IC₅₀s = 0.49-3.1 nM). Topical application of E6005 (0.003-0.3%) reduces ear thickness in a mouse model of oxazolone-induced skin inflammation, as well as reduces oxazolone-induced scratching in mice. It reduces the severity of skin lesions in a model of mite-induced atopic dermatitis. Topical application of E6005 (0.03%) also inhibits the production of leukotriene B₄ (LTB₄; ) in mouse skin, as well as reduces scratching and cutaneous nerve firing induced by the proteinase-activated receptor 2 (PAR2) agonist SLIGRL-NH₂ in mice.