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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, either via transgene expression or CRISPR-mediated locus-specific knock-in. The TAG degrader (e.g. dTAG or aTAG) 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 Degraders page.

TPD Tag Degradation Platform 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 and aTAG 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 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.

dTAG and aTAG Degraders

Our dTAG and aTAG 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 and can be used in cell culture or in vivo.

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.

Degrader mechanism of action

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.

Resources for Target Validation and Exploration

Image of a cell culture flask

Cell Culture Reagents

We offer a full selection of classical media, salt solutions, serum, supplements, and basement membrane extracts, as well as serum-free and xeno-free media for immune cell culture.

Antibodies

Antibodies for Western Blotting

Bio-Techne provides a wide range of antibodies validated for western blot and Simple Western assays.

Validating Targets for Targeted Protein Degradation using dTAG Whitepaper

Validating Targets for Targeted Protein Degradation using dTAG

Check out our whitepaper to 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.

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