Topical Agents and Emerging Perspectives in Psoriasis
E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,10-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione] (Eisai Inc.) is a MEK1/MEKK1 inhibitor exerting a potent anti-inflammatory action suppressing the production of proinflammatory cytokines from leukocytes and keratinocytes. E6201 suppresses in vitro lymphocyte activation and proliferation. An important in vitro effect is the inhibition of neutrophil migration, reflecting the suppression of IL-8 production from activated human keratinocytes. Muramoto et al. observed that topical treatment with E6201 significantly inhibited epidermal hyperplasia in IL-23-treated mice. Moreover, E6201 shows direct antiproliferative activity on cultured keratinocytes; therefore, it may be effective in psoriasis because of distinct effects on both immune cells and keratinocytes.
Using several experimental models of dermatitis, preclinical studies showed that topical administration of E6201 formulated as an ointment or cream was effective in reducing acute edema formation and neutrophil infiltration into mouse skin.
A double-blind, multicenter, Phase II study assessed the efficacy and safety of E6201 topical administration to preidentified marker lesions in patients with chronic plaque-type psoriasis. The duration of treatment was 8 weeks, followed by a 4-week period without treatment.
Another Phase II trial is currently ongoing to determine the efficacy and safety of six concentrations of topical E6201 gel.
MEK1/MEKK1 Inhibitor
E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,10-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione] (Eisai Inc.) is a MEK1/MEKK1 inhibitor exerting a potent anti-inflammatory action suppressing the production of proinflammatory cytokines from leukocytes and keratinocytes. E6201 suppresses in vitro lymphocyte activation and proliferation. An important in vitro effect is the inhibition of neutrophil migration, reflecting the suppression of IL-8 production from activated human keratinocytes. Muramoto et al. observed that topical treatment with E6201 significantly inhibited epidermal hyperplasia in IL-23-treated mice. Moreover, E6201 shows direct antiproliferative activity on cultured keratinocytes; therefore, it may be effective in psoriasis because of distinct effects on both immune cells and keratinocytes.
Using several experimental models of dermatitis, preclinical studies showed that topical administration of E6201 formulated as an ointment or cream was effective in reducing acute edema formation and neutrophil infiltration into mouse skin.
A double-blind, multicenter, Phase II study assessed the efficacy and safety of E6201 topical administration to preidentified marker lesions in patients with chronic plaque-type psoriasis. The duration of treatment was 8 weeks, followed by a 4-week period without treatment.
Another Phase II trial is currently ongoing to determine the efficacy and safety of six concentrations of topical E6201 gel.
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