Degrader Building Blocks
Develop your own Degrader (PROTAC®) with our pioneering range of Degrader Building Blocks. Our extensive library of PROTAC® components enables you to generate Degrader panels rapidly and cost-effectively. Designed by our in-house chemistry experts, the Degrader Building Blocks range includes the most commonly used E3 ligase ligands, conjugated to variable linkers with reactive handles for conjugation to your target protein ligand (warhead ligand) (Figure 1).
Why Buy Degrader Building Blocks From Us?
- We maintain our products in stock for fast delivery;
- Wide range of building blocks available, curated by our in-house experts;
- Bulk discounts and custom synthesis available;
- Don’t see what you need? Easily generate custom panels with our PROTAC® Panel Builder tool on tocris.com.
PROTAC® design typically requires the development, synthesis and screening of panels of candidate Degraders. For a single target protein ligand, a candidate Degrader panel would typically vary by the E3 ligase ligand, exit vector and linker (type and length) used. Our Degrader Building Blocks cover the most commonly used E3 ligase ligands and linkers with functional handles for easy conjugation to your target protein ligand. The range includes functionalized E3 ligase ligands targeting von Hippel-Lindau (VHL), cereblon (CRBN) and inhibitor of apoptosis (IAP) conjugated to linkers comprising PEG or alkyl chains with amine, acid, alkyne, azide or alcohol functionality for onward chemistry.
What are Degrader Building Blocks?
Figure 1: Illustration highlighting the component parts of Degrader Building Blocks. A) Schematic representation of heterobifunctional Degrader (PROTAC®). Degraders are heterobifunctional small molecules comprising binding moieties for an E3 ubiquitin ligase and a target protein connected by a linker. The figure indicates the Degrader mechanism of action via the formation of a ternary complex between the E3 ligase, Degrader and target protein. This results in polyubiquitination of the target protein and subsequent degradation by the 26S proteasome. This Targeted Protein Degradation can be used to investigate downstream effects of protein knockdown or to interfere with specific signaling pathways. B) Schematic representation of a Degrader Building Block. C) Example of a Degrader Building Block, Thalidomide 4'-ether-alkylC4-amine (Cat. No. 6917).
Degrader Design Just Got Easier
Quickly and easily create bespoke panels of Degrader Building Blocks for your Targeted Protein Degradation research with our PROTAC® Panel Builder tool on tocris.com.
For further information, bulk/custom enquiries or to request a sd/sdf file of our Degrader Building Blocks library, contact our experts via TPD@bio-techne.com.
PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
Learn more about developing Degraders in this paper in MedChemComm: Developing Degraders: Principles and Perspectives on Design and Chemical Space
Bondeson, DP et al. (2015) Catalytic protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. PMID: 26075522.
Cromm, PM and Crews, CM (2017) Targeted Protein Degradation: from Chemical Biology to Drug Discovery. Cell Chem. Biol. PMID: 28648379.
Ohoka, N et al. (2017) Knockdown of pathogenic proteins via specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs). J. Biol. Chem. PMID: 28154167.
Smith, BE et al. (2019) Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase. Nat. Commun. PMID: 30631068.