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Degrader Building Blocks

Inhibition of the activity of functional proteins is one of the main strategies for the development of small molecule drugs, and targeted protein degradation is an alternative approach in drug discovery with the aim of reducing the overall levels of disease-associated proteins. While traditional small molecule or antibody drugs only allow access to about -20% of the proteome, degradation techniques are powerful tools to access the remaining 80% of the proteome.

Synthetic targeted protein degradation molecules, commonly referred to as protein hydrolysis targeted chimeras (PROTACs) are designed to modify the disease-causing proteins by altering the ubiquitin-proteasome machinery. In general, PROTACs are designed with two active domains and a linker: the first active domain is the primary ligand that binds to the target protein (POI) for degradation of the drug target, and the second active domain is another ligand that binds to an E3 ubiquitin ligase. The intermediate cross-linker is responsible for connecting these two ligands. These small bifunctional molecules are able to bind to both the target and the ligase, resulting in their spatial proximity. The ultimate goal is to ubiquitinate the target and then degrade it by inducing selective intracellular protein hydrolysis.

Application

  • Accelerate synthesis process

Ligand-linker conjugates help to simplify the synthesis of single degradants and parallel synthesis of library constructs

  • Molecular design

The arrangement of E3 ligands, exit vectors and linkers within the conjugates facilitate the design of combinatorial libraries

  • Compatibility

Linkers are rapidly linked to common functional groups on the target ligands

  • SAR studies

Strategic component changes in ligand-linker conjugates provide important guidance for pre-SAR optimization

Protein degradation.  Figure 1. Protein degradation. (Potjewyd, F.; et al. 2019)

Library Design

BOC Sciences offers a high-quality library design service for PROTAC building blocks consisting of compounds that are highly similar to known target E3 ligases as well as linker-like compounds (PEG, alkyl chains and alkyl/ethers).

  1. Our PROTAC building block library contains over 1,700 compounds designed based on structural and activity data for known PROTACs and E3 ligase binders (2D fingerprint similarity search, Tanimoto index≥0.85) and general structural properties of known PROTAC crosslinkers
  2. The second active PROTAC moiety, which is acting against a specific drug target of interest, can be found in BOC Sciences’ collection of targeted and focused libraries

Degrader Building Blocks Characteristics

  • No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
  • All PAIN and reactive compounds are excluded from selection by internal filter applications
  • Confirmed bioactivity and safety via preclinical studies and clinical trials
  • Structural diversity, significant efficacy, and cellular penetration
  • Structural document, IC50, and other chemical and biological data are provided
  • Tanimoto index ≥ 0.80
  • All compounds are continually updated
  • Compound cherry-picking service is provided

What We Deliver

  • Delivered within 2 weeks in any customer-preferred format
  • Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
  • All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
  • Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Degrader Building Blocks design at competitive prices for global customers. Personalized and customized services of Degrader Building Blocks design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!

Reference

  1. Potjewyd, F.; et al. Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader. Cell Chemical Biology. 2019. 27(1).
Our mission is to provide clients with a professional chemical library design platform. Empowered by high-quality services and effective research solutions, we are committed to helping customers achieve effective and successful research goals.

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Services Based on the Chemical Library Design Platform

Services Based on the Chemical Library Design Platform

BOC Sciences has rich experience in working with global customers in custom library synthesis of compounds and generating small to medium-sized libraries of target compounds. Our knowledge in generating a large number of target molecules in a remarkably shorter time enables quick biological screenings for affinities. With the target properties in mind, we deliver target molecules, by applying our extensive knowledge in drug discovery.

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