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.

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

Materials Tested

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

Request a copy of this paper, click here.