TPD Capabilities
Design and synthesis of molecular glues, PROTACs and other heterobifunctional molecules
During the last decade, the discovery of targeted protein degraders developed and grew into an independent area of research. For a TPD project to move, it is crucial to have access to dedicated libraries for screening, to diverse linker-type building blocks, and to the design and rapid synthesis of intermediates, molecular glues and heterobifunctional molecules. With access to the Enamine Protein Degradation Toolbox as well as to a team of skilled chemists, Enamine Germany is a reliable partner in the design and synthesis of new molecular glues, PROTACs and other heterobifunctional molecules.
- Molecular Glue Space
- 4M+ REAL
- Target Libraries
- CRBN · DCAF · VCL
- E3 Binders
- CRBN · VHL
- Support
- Design to route
Target Libraries
A search for new binders for various E3 ligases is a crucial step in the research of new degraders, and for that it is important to have reliable target libraries. We are ready to provide our off-the-shelf target libraries — CRBN binders, DCAF ligands, VCL — as well as to design a library on request, to your criteria, out of the Enamine screening collection.
Molecular Glues — REAL
Enamine's specialised subset of more than 4M REAL compounds is a unique space for the search of new E3-ligase binders and molecular glues. It can be used for the design of your own screening library as well as for hit follow-up activities and SAR investigation.
Design and Custom Synthesis of PROTACs
Along with the ability to test compounds in validated assays, a campaign to develop potent PROTACs requires strong synthetic chemistry capabilities in combination with CADD support. Our chemists have large experience in the design and synthesis of PROTACs and other heterobifunctional molecules, and are ready to support your project in this fascinating area from design to a validated, reliable synthetic route.
E3 Binders and Intermediates
For the rapid discovery of protein-of-interest degradation it is convenient to have access to building blocks bearing the corresponding E3-ligase binding motif — CRBN, VHL — as well as to intermediates containing E3 binders with attached linkers of different length, composition and rigidity. Access to such building blocks and intermediates is what makes it possible to prepare a series of PROTACs quickly from a discovered POI ligand, or to generate diverse derivatives for new molecular glues. Our specially designed kits of intermediates can be used for rapid and versatile research into POI degradation.
Linkers
Linkers are a key component of PROTACs and other heterobifunctional molecules. Numerous scientific studies suggest that a linker's length, polarity and rigidity can play a crucial role in ternary complex formation, its stability, and the pharmacokinetic properties of the bifunctional molecule. Quick and easy access to various linkers is essential for a rapid linkerology search, since it is next to impossible to predict a perfect linker for a given target. With access to diverse Enamine linkers from the building block collection, and our experience in developing PROTAC molecules, Enamine Germany can be an effective partner in the design and synthesis of linkers and their application within the corresponding heterobifunctional molecules.