Natural product-based compounds demonstrate potent anti-inflammatory and anti-itch effects in a mouse model of atopic dermatitis

Summary: Atopic dermatitis (AD) is a common and debilitating skin disease characterized by inflammation and itch. While the precise molecular pathogenesis of AD is not fully understood, multiple cytokines have been discovered that mediate AD inflammation (such as IL4, IL5, and IL13) and itch (IL31). Despite recent approval of systemic and topical therapies, there is still a significant unmet need for additional safe and effective therapies for AD. To meet this need, our team has developed a group of novel natural-product based small-molecule compounds including DB007-5. In a MC903-induced mouse model of AD, DB007-5 demonstrated strong and concentration dependent inhibition of inflammation score (p<0.05 for 0.5%, 0.75% and 1% concentrations). Further, at 0.75%, DB007-5 reduced scratching (itch) score at Day 12 from 7.2+/-2.70 in vehicle treated group to 0.70+/-0.33, p<0.05), while ruxolitinib 1.5% reduced the scratching score to 1.7+/-0.62, p<0.05). In summary, DB007-5 demonstrated strong anti-inflammatory effects as well as potent inhibition of the primary symptom of AD, namely itch. Further studies are underway to evaluate the potential of DB007-5 as a therapy for AD. Gordon Eberwein¹, Sarah Paris-Robidas², Frederic Couture², Ming-wan Su³, Andy Sham^{4, 1}, Poul H Sorensen^{5, 1}, Youwen Zhou^{1, 3} 1. Derm-Biome Pharmaceuticals, Inc, Vancouver, BC, Canada. 2. TransBIOTech, Levis, QC, Canada. 3. Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada. 4. BC Children's Hospital Research Institute, Vancouver, BC, Canada. 5. Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Translational Studies: Preclinical