BACKGROUND: UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole] is a small-molecule tumour necrosis factor (TNF)-alpha modulator being investigated for its potential in several immune-mediated diseases, including psoriasis. OBJECTIVES: We aimed to determine whether UTL-5d represents a potential antipsoriasis agent. METHODS: Firstly, a keratinocyte cell-based study was used to study the inhibition of TNF-alpha and gene suppression by UTL-5d in vitro. Secondly, a multilayered human epidermis tissue model, consisting of normal human-derived epidermal keratinocytes, was used to study the dose-dependent reduction of TNF-alpha by UTL-5d as well as the feasibility of using UTL-5d in a lotion formulation. RESULTS: The cell-based study showed that UTL-5d significantly reduced TNF-alpha secretion from keratinocytes (68% reduction at 17 mug mL(-1)) and suppressed JAK3 and MAP3K2 genes by 70% and 40%, respectively. In the human epidermis tissue model, reduction of TNF-alpha by UTL-5d appeared to be dose dependent (8.35-33.4 microg mL(-1)); UTL-5d also reduced cell death induced by ultraviolet (UV) B. Tissues treated by UTL-5d in a preliminary lotion formulation showed significant reduction of TNF-alpha induced by UVB. CONCLUSIONS: Our results indicate that UTL-5d may be worthy of further investigation for its potential as a topical agent for psoriasis.
BACKGROUND: UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole] is a small-molecule tumour necrosis factor (TNF)-alpha modulator being investigated for its potential in several immune-mediated diseases, including psoriasis. OBJECTIVES: We aimed to determine whether UTL-5d represents a potential antipsoriasis agent. METHODS: Firstly, a keratinocyte cell-based study was used to study the inhibition of TNF-alpha and gene suppression by UTL-5d in vitro. Secondly, a multilayered human epidermis tissue model, consisting of normal human-derived epidermal keratinocytes, was used to study the dose-dependent reduction of TNF-alpha by UTL-5d as well as the feasibility of using UTL-5d in a lotion formulation. RESULTS: The cell-based study showed that UTL-5d significantly reduced TNF-alpha secretion from keratinocytes (68% reduction at 17 mug mL(-1)) and suppressed JAK3 and MAP3K2 genes by 70% and 40%, respectively. In the human epidermis tissue model, reduction of TNF-alpha by UTL-5d appeared to be dose dependent (8.35-33.4 microg mL(-1)); UTL-5d also reduced cell death induced by ultraviolet (UV) B. Tissues treated by UTL-5d in a preliminary lotion formulation showed significant reduction of TNF-alpha induced by UVB. CONCLUSIONS: Our results indicate that UTL-5d may be worthy of further investigation for its potential as a topical agent for psoriasis.
Authors: Jiajiu Shaw; Brian Shay; Jack Jiang; Frederick Valeriote; Ben Chen Journal: Eur J Drug Metab Pharmacokinet Date: 2011-11-05 Impact factor: 2.441
Authors: Jiajiu Shaw; Ben Chen; Jean P Bourgault; Hao Jiang; Narendra Kumar; Jayshree Mishra; Frederick A Valeriote; Joe Media; Kevin Bobbitt; Halina Pietraszkiewicz; Matthew Edelstein; Peter R Andreana Journal: Am J Biomed Sci Date: 2012