610 Identification of the selective glucocorticoid receptor agonist Mapracorat as potential new drug for chronic wound therapy

We have shown that the effects of wound exudates on fibroblast cultures reflect their clinical healing phenotype and can thus serve as a functional biomarker. used this assay for screening to identify compounds or compound classes with so far unknown potential chronic therapy. The selective glucocorticoid receptor agonist (SEGRA) Mapracorat was found reverse inhibitory effect several exudates. profiled in additional exudate-based cellular assays investigate its suitability Primary human dermal fibroblasts were grown 384-well plates 2D 3D cultures. added cells presence from different patients. Incubation times 72 hours 4 – 8 days Supernatants then harvested determination IL-1beta, RNA extracted RT-PCR, fixed stained protein. rescued inhibition exudate-induced proliferation 80% 200 tested. For 95/200 wounds etiologies, cell increased by >150% compared exudate alone, complete recovery demonstrated 25% these samples. This rescue achieved at low nanomolar concentrations. dose-dependently inhibited IL-1beta production enhanced matrix formation well collagen 1 3 mRNA expression, indicating transition chronic/non-healing ex vivo. In vivo wounds, reversed detrimental formation, reduced proinflammatory cytokine secretion. showed good excellent activity almost 50% To select patients best suited therapy compound, theranostic pretesting is recommended.