View Featured Offers >>

Solutions for Targeted Protein Degradation

Targeted protein degradation (TPD) is a therapeutic approach that uses the cell’s own destructive machinery to break down proteins that cause or drive disease progression. Many of these target proteins lack certain characteristics, like a defined pocket for effector protein interaction, and are “undruggable” using conventional methods. Protein degrader platforms like PROteolysis TArgeting Chimeras (PROTACs), and molecular glue degraders utilize the ubiquitin-proteasome pathway to initiate degradation while platforms like autophagosome-tethering compound (ATTECs), AUTOphagy-TArgeting Chimeras (AUTOTACs), AUtophagy-TArgeting Chimeras (AUTACs), and antibody-based PROTACs (AbTACs), and LYsosome TArgeting Chimeras (LYTACs) leverage the autophagosome or lysosome system. These platforms, along with other TPD modalities, can target previously undruggable proteins for degradation by creating a bridge between the protein of interest and the effector molecule, leading to new strategies for potential targeted drug therapies for a wide range of diseases.

Scientists at Cell Signaling Technology have deep signal technology expertise and can assist you with understanding the on- and off-target effects of your TPD treatment. You can also access a broad catalog with a wide range of products, along with industry-leading proteomic services, than can help you streamline different steps in the TPD discovery workflow, enabling you to better validate a potential TPD molecule.

Targeted Protein Degradation (TPD) Products and Services

Overview

The TPD drug discovery workflow. (Step 1) Design a degrader that can bind to an E3 ligase and the target protein. (Step 2) Confirm that the degrader forms a ternary complex with the E3 ligase and target protein. (Step 3) Check for target protein polyubiquitination. (Step 4) Quantitate target degradation. (Step 5) Investigate on- and off-target effects to understand the phenotypic consequences of degrading the target protein.

Degrader Discovery

Degrader Discovery

Identify the target protein driving disease progression and the associated E3 ubiquitin ligase in cells or tissues of interest using the following products.

  • Target Protein Antibodies: Specific, application-validated antibodies for potential targets including:
  • E3 Ligase Antibodies Specific antibodies recognizing E3 ligases such as CRBN, VHL, KEAP1, and MDM2 are validated for your platform. Refer to the Ubiquitin Ligase Table for a list of E3 ubiquitin ligases and their known substrates.
  • Proteomics Analytical Services Profile key proteins and post-translational modifications to quickly ID potential targets and E3 ubiquitin ligases with the help of CST Proteomics Analytical Services. These services offer chemical-proteomics to identify reactive cysteines in complex proteomes for covalent-inhibitor drug development, allowing you to uncover novel cysteines that modulate protein function or help identify cellular targets susceptible to electrophilic warheads.
  • Cysteine Profiling: Map out reactive amino acid side chains on proteins of interest in the context of complex biological systems. Receive an optimized workflow solution using reactive cysteine labeling, along with peptide enrichment mass spectrometry analysis to efficiently identify and quantify accessible, reactive cysteine sites on important protein targets.

Ternary Complex Formation

Ternary Complex Formation

Investigate ternary complex formation using TR-FRET, co-immunoprecipitation, and AlphaLISA to determine the binding efficiency of your TPD molecule and find out if the proximity between the E3 ligase and your target protein is optimal for ubiquitin transfer.

CST offers validated and reproducible off-the-shelf solutions, including tagged antibodies and matched antibody pairs, to support ternary complex formation experiments. Don’t see the conjugation or formulation you need for your platform? CST can develop, optimize, and validate it for you.

  • Custom Conjugation Services: CST has highly experienced custom conjugation experts that you can lean on. If you don’t see the conjugated antibody you need for your platform in our catalog, we’ll conjugate it to a metal, fluorophore, biotin, or DIG for you. Review the Resources and Guides for Antibodies Compatible with Your Assay Platform to find the conjugation that will work for your platform.
  • Matched Antibody Pairs: Carrier-free, conjugation-ready Matched Antibody Pairs have been optimized for you and are ready for your TR-FRET assays.
  • Customized Formulations for Immunoassay Development: Order BSA-, azide-, and glycerol-free antibody formulations for your ELISA-like assays and in vivo functional assay development.
  • Anti-Tag Antibodies: Pull down transfected, recombinant tagged proteins in co-immunoprecipitation experiments with specific, sensitive CST® tagged antibodies.
  • Proteomics Analytical Services: Qualitatively and quantitatively profile proteins in your sample. CST scientists can perform tandem mass tag (TMT) assays to assess protein-protein interactions and Proximity Labeling (TurboID/BioID) to confirm ternary complex formation for you.

Target Ubiquitination

Target Ubiquitination

Confirm the ubiquitination of your target protein with CST proteostasis antibodies, or obtain a comprehensive view of all ubiquitination sites on your target protein using either a PTMScan® Ubiquitin kit or by utilizing CST Proteomic Analytical Services.

Target Degradation

Target Degradation

Qualitatively and quantitatively monitor levels of your target protein after a TPD treatment experiment by using any one of a wide variety of specific and sensitive antibodies available in the CST catalog.

Application-validated antibodies for transcription factors, receptor tyrosine kinases, serine/threonine kinases, nuclear receptors, lymphocyte signaling, Jak/Stat proteins, Bcl-2 family proteins, Parkinson’s disease-related proteins, and more are ready to aid your target degradation experiments.

You can find high-quality antibodies against your target of interest that have been validated and approved for use in some of the following applications:

Additionally, off-the-shelf or customized carrier-free antibodies are available for high-throughput ELISA-like platforms. Need a specific conjugation for your platform? Custom conjugation services are also available.

If you are targeting a mutant version of a protein such as EGFR, search through the CST catalog of mutant-specific antibodies. Don't see the protein mutation you are looking for? Contact us about developing, optimizing, and validating it for you.

On/Off Target Effect

On/Off Target Effect

Get a broad molecular understanding of the off-target effects of your TPD molecule by utilizing CST Proteomics Analytical Services.

Work with a CST scientist to perform the following:

  • Proteomics Discovery Services:
    • PTMScan Discovery Proteomic Services Depending on your target of interest, perform a comprehensive PTM analysis for ubiquitinated, phosphorylated, acetylated, and methylated proteins in your sample to monitor the downstream effects of a TPD molecule.
    • KinomeView® Service Identify areas of the kinome that are modulated upon TPD molecule treatment when targeting a kinase.
  • Total Proteomic Profiling:
    • Gain insight into the downstream effects of a TPD molecule and determine potency with time-course studies.
    • Understand the on-target specificity of a TPD molecule and off-target cross reactivity.
  • UbiScan–Ubiquitination Proteomics Quantitatively profile thousands of non-redundant ubiquitinated sequences with LC-MS/MS to identify off-target proteins being undesirably targeted for proteasomal degradation.

Or use one of the following CST kits:

Show More

Resources