Over the last decade, kinases have emerged as attractive therapeutic targets in inflammatory diseases. Numerous efforts in the pharmaceutical community are directed towards the discovery of small molecule inhibitors that regulate kinase function.A number of issues need to be addressed when considering kinases as targets in inflammation. The combination of efficacy and favourable safety profile is often key for the successful treatment of chronic inflammatory and/or autoimmune diseases with kinase inhibitors.The LSE (Low Systemic Exposure) approach is a Creabilis proprietary technology that generates innovative molecules with unique physico-chemical and pharmacological characteristics. LSE molecules are ‘topical by design’ molecules that share some common features. They combine high local concentration with poor systemic absorption and distribution. If absorbed, LSE molecules are rapidly eliminated from the systemic circulation (very short plasma half-life), thus generating no/low side effects. LSE approach has already been clinically validated through CT327, a selective topical kinase inhibitor that recently reported positive Phase 2a data in both psoriasis and atopic dermatitis.This project will combine Creabilis experience and know-how on LSE modification of molecules with the sound systems biology and network pharmacology expertise of the University of Dundee to generate and bring to preclinical development a new generation of innovative molecules optimised for topical treatment of inflammatory diseases, such as psoriasis, atopic dermatitis and inflammatory bowel disease.The generated lead compound(s) will be characterized by minimal or no systemic toxicity combined with efficacy and optimised selectivity. This would tremendously widen the range of patients affected by inflammatory pathologies that could benefit of topical kinase inhibition as a therapy and provide an innovative concept for new medicines to be developed.