Cancer is in many respects a disease in which cellular transcription is deregulated. Transcription factors are therefore often potent oncogenes that strongly promote the growth of cancer cells. Our strategy is therefore to correct these altered transcription patterns with the help of small molecules. Many transcription factors cannot be attacked directly by small molecules. However, their activity can be indirectly modulated by targeted interventions in their regulation or the underlying transcription machinery.

As part of our consortium, we deliberately cover projects at different stages of drug development, utilizing the complementary expertise and technologies at the various sites integrated into TACTIC. Our extensive target protein portfolio includes target structures such as kinases that are well established as drug targets, but also small molecule addressable transcription factors that have ligand-binding structured domains as well as highly innovative target structures such as regulators of chromatin structure and mRNA splicing.

Conventional small molecules as well as new modalities such as bifunctional molecules like PROTACs (PROteolysis Targeting Chimeras), which specifically degrade the target structure, are used. In order to develop PROTACs efficiently, a click chemistry-based high-throughput PROTAC screening platform is currently being established, which will enable many of these molecules to be synthesized in parallel on a very small scale and tested directly in cellular systems. Synergistically, we are expanding our patient-based cell banks, which cover diverse tumor types, and developing disease-relevant in vivo models for systematic drug screening and mechanistic studies.