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Solutions for Targeted Protein Degradation

Tools for Proximity-Induced Targeted Protein Degradation

Proven Solutions to Increase Productivity in Your TPD Workflow

Get the trustworthy tools and support you need to move your targeted protein degradation (TPD) project forward. CST offers a comprehensive suite of platform-compatible, application-validated tools to answer critical questions at every stage of TPD drug development. And our in-house manufacturing means you can count on reliable supplies.

With an unmatched range of top-tier products backed by technical rigor, CST^® solutions help reduce risks in assay implementation, increase data confidence, and improve productivity on platforms you already use.

Targeted Protein Degradation Solutions from CST

A diagram showing six steps in a workflow to develop a targeted protein degradation drug

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Degrader Discovery

Optimize degrader design and identify the associated E3 ubiquitin ligase for your target molecule in cells or tissues of interest.

A diagram showing a protein, a degrader molecule, and an E3 ligase all separated from each other

Experimental Goal	Method	CST Solutions
To measure abundance of E3 ubiquitin ligases in cells or tissue of interest	Using specific antibodies to detect E3 ubiquitin ligases and their components	CRBN, VHL, Additional E3 Ubiquitin Ligases PROTAC E3 Ligase Profiling Antibody Sampler Kit CRL4/CRBN Targeted Protein Degradation Complex Antibody Sampler Kit
To discover accessible, nearby reactive residues on my protein of interest that can improve the binding of my degrader	Reactive cysteine mapping/profiling using mass spectrometry	Proteomics Analytical Services Proteomics Service Inquiry

Experimental Goal

Method

CST Solutions

To measure abundance of E3 ubiquitin ligases in cells or tissue of interest

Using specific antibodies to detect E3 ubiquitin ligases and their components

CRBN, VHL, Additional E3 Ubiquitin Ligases

PROTAC E3 Ligase Profiling Antibody Sampler Kit

CRL4/CRBN Targeted Protein Degradation Complex Antibody Sampler Kit

To discover accessible, nearby reactive residues on my protein of interest that can improve the binding of my degrader

Reactive cysteine mapping/profiling using mass spectrometry

Proteomics Analytical Services
Proteomics Service Inquiry

Ternary Complex Formation

Investigate ternary complex formation with assays designed to demonstrate physical proximity between an E3 ligase and your target protein. Optimal ternary complex formation is essential for efficient ubiquitination of the protein of interest(POI) and UPS-mediated degradation.

A diagram showing a protein, a degrader molecule, and an E3 ligase all bound to each other

Experimental Goal	Method	CST Solutions
To confirm that the degrader forms a ternary complex with the E3 ligase and target protein	TR-FRET immunoassays	Europium Cryptate Antibody Conjugates Alexa 647 Antibody Conjugates Custom Europium Cryptate Labeling Services for TR-FRET Assays
		Pair-based immunoassay tools	Matched Antibody Pairs ELISA-validated Antibodies Custom Conjugation & Labeling Services
		Biochemical assays	Anti-Tag Antibodies
		Proximity labeling (TurboID/BioID) LC-MS	Proteomics Analytical Services Proteomics Service Inquiry
To examine reactive cysteine residues on my target protein for covalent adduct formation of my degrader	Reactive cysteine mapping/profiling LC-MS	Proteomics Analytical Services Proteomics Service Inquiry

Target Ubiquitination

Confirm the ubiquitination of your target protein using ubiquitin antibodies, pan-branched ubiquitin profiling, Tandem Ubiquitin Binding Entities (TUBEs), or with a comprehensive view of all ubiquitination sites using LC-MS proteomics.

A diagram showing a protein with several ubiquitin molecules attached

Experimental Goal	Method	CST Solutions
To identify and quantify ubiquitination on my protein of interest	LC-MS-based enrichment, identification, and quantification of ubiquitination	PTMScan^®Ubiquitin Kits Proteomics Analytical Services
		Validated antibodies to specifically detect free or polyubiquitination	Ubiquitin Antibodies Branched Ubiquitin Sampler Kit
		Tandem Ubiquitin Binding Entities (TUBEs)-based profiling of pan ubiquitination	Pan-Branch Ubiquitin TUBEs

Target Degradation

Evaluate the effectiveness of your degrader candidates by directly assaying the levels of your target protein after treatment using specific and sensitive antibodies. Or take advantage of deep proteome profiling offered by CST Proteomics Analytical Services.

A diagram showing a protein that has been digested by the proteasome.

Experimental Goal	Method	CST Solutions
To find out whether the protein of interest has been degraded	Simple Western WB	Simple Western-validated Antibodies WB-validated Antibodies
		ELISA	ELISA Kits Matched Antibody Pairs ELISA-validated antibodies BSA- & Azide-Free Antibodies Europium conjugates for TR-FRET
		High-Content Imaging, Analysis, and Screening (HCI/HCA/HCS)	High Content-validated Antibodies
		Antibody conjugates	Antibody Conjugates Custom Labeling Services
		Deep proteome profiling using DIA Mass Spectrometry	Proteomics Analytical Services Proteomics Service Inquiry

Identify On-/Off-Target Effects

Obtain a broad molecular understanding of the on- and off-target effects of your TPD molecule using LC-MS proteomics.

A diagram showing a protein that has been digested by the proteasome using different colors to represent potential on- and off-target effects.

Experimental Goal	Method	CST Solutions
To examine on- and off-target effects of a specific degrader	Monitor on- and off-target protein degradation	Global Proteome Profiling
		Identify and quantify sites of ubiquitination for on- and off-target validation	Ubiquitin Proteome Profiling PTMScan Ubiquitin Kits
		Survey downstream effects of TPD dosing	PTM Proteomic Profiling PTMScan Motif Antibody Kits

Phenotypic Response

Examine the resulting cellular morphology and protein localization of targets along with different cellular and tissue-based phenotypic readouts and markers.

Experimental Goal	Phenotypic Markers and Readouts
Downstream cellular and tissue-based phenotypic changes after degrader treatment	Oncology Neurodegenerative Diseases Cellular Assay Kits

About Targeted Protein Degradation

Targeted protein degradation is a versatile therapeutic approach that uses the cell’s own destructive machinery to degrade proteins of interest (disease drivers). TPD is attractive as a therapeutic modality because many proteins of interest lack features (e.g., binding pockets) that can be targeted by traditional small molecule therapies, rendering them “undruggable” by conventional methods. These platforms, along with other TPD modalities, can target previously undruggable proteins for degradation by inducing proximity-based interactions between the protein of interest and an effector molecule, opening the door to the potential development of targeted drug therapies for a wide range of diseases.

Common degrader molecule chemistries include:

PROTAC
ATTEC
AUTOTAC
AUTAC
AbTAC
LYTAC

Resources

Targeted Protein Degradation Webinar
Data Independent Acquisition Proteomics Flyer
Data Independent Acquisition Proteomics Blog
Simplifying Proteomics Brochure
Custom Products and Services Flyer
Custom Conjugation Flyer
Matched Antibody Pairs Flyer
Simple Western Flyer
Custom Labeling Service Request Form
Proteomics Analytical Services Request Form