Target Validation and Targeted Protein Degradation

Target validation is the process of establishing that a potential molecular target is involved in a physiological function or disease mechanism. Target identification and validation are important steps in drug discovery and biological research. Target validation can be achieved by modulation of a potential target and exploring the downstream molecular and/or phenotypic consequences. Protein Degraders and the field of Targeted Protein Degradation offer a differentiated way to modulate target proteins using small molecules. While a small molecule inhibitor will block or modulate a specific protein domain or function (for example an enzymatic role), a small molecule Degrader will knockdown the entire protein, removing all possible functions. Target validation is therefore an important stage of the Degrader development project workflow. The validation of a protein target then supports the design and chemical synthesis of a Degrader or other small molecules selective for that target.

Bio-Techne has a range of tools available for target identification and validation including our TAG Degradation Platform and Protein Degraders.

TAG Degradation Platform for Target Validation

TAG Degradation technology offers a generalizable strategy to degrade, in principle, any intracellular protein of interest. This target validation methodology requires a protein of interest to be expressed as a fusion protein with a TAG domain, also known as a degron tag, either via transgene expression or CRISPR-mediated locus-specific knock-in. The small molecule TAG Degrader (e.g. dTAG, aTAG or BromoTag®) recruits the fusion protein for ubiquitination by an E3 ligase, which targets it for destruction by the proteasome.

For more information on how TAG Degradation works, check out the dTAG/aTAG/BromoTag Degraders page.

TAG degradation workflow
Figure 1. TAG Degradation Platform Workflow.

Bio-Techne offers a full range of products and services across the TAG Degradation Platform Workflow including Custom knock-in TAG Cell Lines, dTAG, aTAG and BromoTag Degraders, as well as Simple Western™ instruments and validated antibodies for western blotting to measure target protein knockdown.

Products and Services for the TAG Degradation Platform

Cell Engineering Services graphic

Cell and Gene Therapy Services

We offer fully customizable cell line development services utilizing our TcBuster™ gene transfer system and traditional methods to engineer your desired cell line. We can engineer any cell type with aTAG or dTAG knockins, SNP edits, and insertion of large genes of interest. We specialize in complex projects and hard-to-transfect cell lines.

Bio-Techne, through its Tocris brand, offers agonists, antagonists, and other small molecules for a range of research areas.

dTAG, aTAG and BromoTag Degraders

Our dTAG,  aTAG and BromoTag Degrader molecules target fusion proteins comprising your target of interest fused to a protein tag. This technology allows rapid and highly selective degradation of a protein of interest and offers a useful alternative to genetic methods for target validation. It can be used in cell culture or in vivo.

Jess Simple Western instrument by ProteinSimple, a Bio-Techne brand

Simple Western

Detect Degrader-induced knock-down of your target protein of interest with Simple Western. Our Simple Western platforms automate the entire protein separation and detection process, enabling you to accurately measure DC50 and Dmax.

Protein Degraders

Bio-Techne provides a large catalog of off-the-shelf Protein Degraders (including: PROteolysis Targeting Chimeras or PROTAC® molecules; SNIPERs; PHOTACs and uSMITE™ molecules) for a wide range of target proteins. Targeted protein degradation does not always phenocopy inhibition and Protein Degraders often display an enhanced selectivity profile compared to the warhead inhibitor used. Our Protein Degraders are therefore a highly useful tool to explore and validate target proteins and can be used to investigate the phenotypic consequences of proteasome-mediated protein knock-down.

Our Catalog of Protein Degraders

Resources for Target Validation and Exploration

Image of a cell culture flask

Cell Culture Reagents

Learn about our comprehensive workflow solution for target validation in targeted protein degradation using the TAG Degradation Platform. The whitepaper provides  guidance on TAG knock-in cell-line generation, using dTAG Degraders to knockdown your protein of interest, and assays for protein degradation using Simple WesternTM instruments and western blot-validated antibodies.

Antibodies

Antibodies for Western Blotting

Our paper with C4 Therapeutics highlights the use of the AchillesTag (aTAG) targeted protein degradation technology to control Chimeric Antigen Receptor (CAR-T) activity.

Whitepaper: Validating Targets for TPD using dTAG

Learn about our comprehensive workflow solution for target validation in targeted protein degradation using the TAG Degradation Platform. The whitepaper provides  guidance on TAG knock-in cell-line generation, using dTAG Degraders to knockdown your protein of interest, and assays for protein degradation using Simple WesternTM instruments and western blot-validated antibodies.

Research Paper: Development of an AchillesTAG Degradation System

Our paper with C4 Therapeutics highlights the use of the AchillesTag (aTAG) targeted protein degradation technology to control Chimeric Antigen Receptor (CAR-T) activity.

PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.

BromoTag® is a registered trademark of the University of Dundee and is used under license