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Updated: Jul 14, 2026
Separation of Rat Epidermis and Dermis with Thermolysin to Detect Site-Specific Inflammatory mRNA and Protein
Published on: September 29, 2021
Inhibition of tumour necrosis factor-alpha secretion from EpiDermTM tissues by a novel small molecule, UTL-5d
1Unitech Pharmaceuticals, Inc., 4370 Varsity Drive, Ann Arbor, MI 48108, USA. shaw@unitechpharma.com
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.
