Project Details
Projekt
Identification of FKBP-Recruiting Molecular Glues with a Tailored DNA-Encoded Non-Peptide Macrocycle Library (DEL2Glues)
Subject Area
Pharmacy
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 573610216
The overarching goal of this project is to identify molecular glues (MG) as best- or first-in-class ligands for challenging and/or previously undruggable target proteins. Using tailor-made, macrocyclic DELs based on FKBP12 as a presenter protein, we aim to: (i) obtain more, more potent and more drug-like molecular glue hits for previous FKBP12-glued targets; (ii) identify molecular glues for challenging and/or currently undrugged proteins, including targets previously refractory to molecular glue screens. DNA-encoded libraries allow the screening of vastly larger compound numbers compared to previous approaches. The macrocyclic design will preorganize the target protein-facing part of the molecule and can enhance the drug-like profile of the molecular glues. Compared to previous FKBP12 glue- or FKBP12 macrocycle and/or FKBP12 glueDEL libraries, the compounds explored in this project will be substantially more drug-like (smaller and less H-donors), and will have a substantially higher affinity for FKBP12, thus addressing two important chemistry-related limitations of current MG-focused strategies.
DFG Programme
Research Grants
Co-Investigators
Professor Dr. Stefan Knapp; Dr. Hans Michael Maric
