Category: Assay Development and Screening
IL17 and its various isoforms have been shown to play a critical role in the development and maintenance of a variety of autoimmune diseases including psoriasis and psoriatic arthritis. Biologics targeting IL-17 have demonstrated impressive clinical response rates for psoriasis. Because the competitive landscape around IL-17 biologics is crowded, we are searching for small molecule targets downstream of IL-17 with the potential for oral dosing or topical application. The purpose of the present study was to build a phenotypic screen to discover potential signaling nodes downstream of IL17 that contribute to disease pathogenesis. A screen was executed using a combination of IL17 and TNFa as stimuli on primary human epidermal keratinocytes measuring IL8 and CXCL1 as read outs. A focused collection of ~22,000 compounds was screened and identified hits modulating the IL17 signaling pathway. The presentation will highlight the design of cellular models, screening workflow, and follow up studies for prioritizing hits and target identification efforts. The power of annotated chemical libraries in phenotypic screening to identify novel targets or mechanisms of action will also be discussed.
Steve Pratt– Sr. Scientist ll, AbbVie, North Chicago, IL