Moriz Mayer

Abstract High-resolution 3D structural information is crucial for drug discovery and routinely used in structure-guided optimization to improve initial hits from screening campaigns to clinical drug candidates. X-ray crystallography is commonly the method of choice to guide medicinal chemistry in the design process, but it has its limitations and shortcomings.

1 INTRODUCTION Transcription factors (TFs) play a critical role in cellular processes and represent a highly relevant target class for drug discovery, given their association with a wide range of diseases, including cancers and developmental disorders.[1, 2] TFs directly regulate gene transcription by binding to specific DNA sequences, serving as a crucial link between cell signaling and gene regulation.[3] Often functioning as (hetero-) dimers, two TFs cooperatively bind to maintain their...

Abstract Aberrant WNT pathway activation, leading to nuclear accumulation of β‐catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β‐catenin and subsequent nuclear translocation. Restoring cellular degradation of β‐catenin represents a potential therapeutic strategy.