CDK4/6 Inhibitoren

Targeting CDK4/6 for the treatment of skin diseases

01.07.2023 bis 30.06.2027

In this project (B09 Kramer/Gehringer), which is part of the SFB/Transregio 156 “The skin as sensor and effector organ orchestrating local and systemic immunity” (3rd funding period), we will develop inhibitors of the protein kinases CDK4 and CDK6 for the treatment of skin diseases. In the previous funding period, the Kramer group has shown that CDK4/6 inhibition can cure experimentally induced psoriasis in mice by suppressing IκBζ expression. The currently available CDK4/6 inhibitors, however, have been developed as orally available anticancer drugs with significant side effects. In this project, we will a) further investigate the role of CDK4/6 in healthy skin and in skin diseases and b) optimize CDK4/6 inhibitors by means of Medicinal Chemistry for topical application. In the first part of this optimization process, we will systematically modify CDK4/6 inhibitors to fine-tune their physicochemical properties for skin uptake. In the second part, “soft drugs” will be generated to minimize systemic side effects. In the end, our project will not only reveal new insights into the role of CDK4 and CDK6 in the skin but also potentially deliver an optimized CDK4/6 inhibitor for topical treatment of skin diseases, such as psoriasis.