452. INHIBITION OF TUMOUR NECROSIS FACTOR-Á SECRETION FROM EPIDERM TISSUES BY A NOVEL SMALL MOLECULE, UTL-5D.

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Shaw¹, J., Liu¹, C., Martin¹, R., Chen², B., Holtz³, R., Huanq⁴, W.H, Lee⁴, A.R. ¹Unitech Pharmaceuticals, Inc., 4370 Varsity Drive, Ann Arbor, MI 48108, USA, ²Department of Internal Medicine, Wayne State University, Detroit, MI, USA, ³BioInnovation Laboratories, Inc., Lakewood, CO, USA, ⁴School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Br. J. of Dermatology, 157, 575-579, (2007).

Summary:
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.

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EpiDerm Data Sheet

EpiDerm Specifications

EpiDerm Technical References

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Applications: Autoimmune disease, Inflammation - skin, Psoriasis

Keywords: Anti-psoriasis agent, EpiDerm, Psoriasis, TNF-a, Tumour necrosis factor alpha modulator

Materials Tested: Eucerin® lotion, PEG 600, UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole], UVB, UVB treatment

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