INHIBITION OF TUMOUR NECROSIS FACTOR-Á SECRETION FROM EPIDERM TISSUES BY A NOVEL SMALL MOLECULE, UTL-5D.
This study by scientists at Unitech Pharmaceuticals, Wayne State University, BioInnovation Laboratories, and the Taiwan National Defense Medical Center demonstrated that MatTek’s EpiDerm in vitro 3-D human skin tissue equivalent could be used to study the dose-dependent reduction of TNF-á by a specific small molecule, UTL-5d, as well as study the feasibility of using this small molecule in a lotion formulation as an anti-psoriasis medication. BACKGROUND: UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole] is a small-molecule tumour necrosis factor (TNF)-á modulator being investigated for its potential in several immune-mediated diseases, including psoriasis. OBJECTIVES: Scientists at Unitech Pharmaceuticals, Inc., Wayne State University, BioInnovation Laboratories, Inc., the Taiwan National Defense Medical Center attempted to determine whether UTL-5d represents a potential anti-psoriasis agent. METHODS: Firstly, a keratinocyte cell-based study was used to study the inhibition of TNF-á and gene suppression by UTL-5d in vitro. Secondly, EpiDerm™, a multi-layered human epidermis tissue model, consisting of normal human-derived epidermal keratinocytes, was used to study the dose-dependent reduction of TNF-á 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-á secretion from keratinocytes (68% reduction at 17 µg mL-1) and suppressed JAK3 and MAP3K2 genes by 70% and 40%, respectively. In the EpiDerm human epidermis tissue model, reduction of TNF-á by UTL-5d appeared to be dose dependent (8.35-33.4 µg mL-1); UTL-5d also reduced cell death induced by ultra-violet (UV) B. Tissues treated by UTL-5d in a preliminary lotion formulation showed significant reduction of TNF-á induced by UVB. CONCLUSIONS: Results indicated that UTL-5d may be worthy of further investigation for its potential as a topical agent for psoriasis.
Anti-psoriasis agent, EpiDerm, Psoriasis, TNF-a, Tumour necrosis factor alpha modulator
Eucerin® lotion, PEG 600, UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole], UVB, UVB treatment
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