TPD Capabilities
During the last decade, the discovery of Targeted Protein Degraders (TPD) developed and grew into an independent area of research. For the successful TPD project promotion it is crucial to have access to the dedicated libraries for screening, diverse linker-type Building Blocks as well as design and rapid synthesis of different 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.
Target Libraries. A search for new binders for various E3-ligases is a crucial step in the research of new degraders. For these purposes, it is important to have reliable target libraries. We are ready to provide our off-the-shelf target libraries (e.g. CRBN-binders, DCAF-ligands, VCL) as well as design the library upon your request and using your criteria based on Enamine Screening for Collection.
Molecular Glues-REAL. Enamine specialized subset of +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 its own unique 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 in the development of 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 validating the reliable synthetic route.
E3-binders and Intermediates E3-binder/linkers. For the rapid discovery of Protein of Interest (POI) degradation, it is convenient to have access to various Building Blocks bearing the corresponding E3-ligase binding structural motif (e.g. CRBN, VHL) as well as intermediates containing E3-binders with attached linkers of different lengths, composition, and rigidity. Access to such Building Blocks and intermediates is necessary for the rapid preparation a series of PROTACs based on discovered POI-ligand or generation of diverse derivatives for the development of new Molecular Glues. Our specially designed kits with different intermediates can be used for rapid and versatile research of POI degradation.
Linkers belong to the key component of PROTACs and other heterobifunctional molecules. Numerous scientific studies suggest that the linker’s length, polarity, and rigidity can play a crucial role in the tertiary complex formation, its stability, and the pharmacokinetic (PK) properties of the bifunctional molecules. 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 based on the Building Block collection and our vast experience in the development of PROTAC molecules, Enamine Germany can be an effective partner in the design and synthesis of linkers and their application within the corresponding heterobifunctional molecules.
