JAK proteins are key signaling molecules of several cytokine receptors. Oral JAK inhibitors are approved for the treatment of cancer and inflammatory diseases in which they have proven to be efficacious but also to exhibit significant adverse events related with immune-suppression, thromboembolism, gastrointestinal perforations and alterations in laboratory parameters.<br/>Topical drug delivery presents a huge opportunity for the treatment of inflammatory dermatological diseases. Topical treatment with JAK inhibitors may cause local immunomodulation and lesion improvement, with a significant reduction or avoidance of systemic side effects previously described. This is particularly relevant in indications such as atopic dermatitis, which is a pediatric indication demanding large safety margins. Thus, a comprehensive medicinal chemistry exercise for the optimization of a series of aminopyrimidines that led to the discovery of LAS200019 as a topical clinical candidate for the treatment of inflammatory skin diseases will be presented. Key aspects of the development of topical drugs such as phototoxicity risk and solubility in topically relevant solvents will be addressed.

Discovery of LAS2000019, a novel topical JAK inhibitor for the treatment of inflammatory skin diseases

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.