Targeted Protein Degradation (TPD) Omics Analysis Service
Targeted Protein Degradation (TPD) drugs exhibit significant potential in targeting traditionally challenging and undruggable protein targets, garnering considerable attention within the scientific community. In addition to the well-known PROTACs (Proteolysis Targeting Chimeras), there is a burgeoning development of alternative strategies, including Molecular Glues, Click Chemistry-based Proteolysis Targeting Chimeras (CLIPTAC), Specific and Non-genetic IAP-dependent Protein Erasers (SNIPER), Hydrophobic Tags, and a variety of innovative PROTAC variants such as Photopharmacology-based PROTACs (PHOTAC), Semiconductor Polymer Nanotechnology PROTAC (SPNpro), flote-PROTACs, Antibody-PROTAC conjugates, Antibody-based PROTAC (PROTAB / AbTAC), Ribonuclease Targeting Chimera (RIBOTAC), Transcription Factor PROTAC (TF-PROTAC), Chaperone-Mediated Protein Degradation (CHAMP), and bioPROTACs. This field is rapidly expanding and entering a phase of explosive growth.
Off-target toxicity has always been a critical factor influencing the success of drug development. Traditional small molecule inhibitors primarily suppress protein activity, meaning that even if some off-target effects occur, the affected proteins can often still retain sufficient energy to maintain cellular function. However, Targeted Protein Degradation (TPD) drugs function by directly degrading target proteins, posing significant risks of off-target cellular toxicity. A classic example is the teratogenic incident involving thalidomide, a drug that unintentionally caused toxicity by degrading essential proteins. Molecules based on the structure of thalidomide-like analogs have become commonly used components in PROTAC molecules. Nonetheless, the toxicity of thalidomide serves as a persistent reminder to developers about the heightened importance of addressing toxicity in TPD drugs.
Proteomics technology plays a crucial role in detecting changes in the abundance of thousands of proteins in cell lines before and after TPD treatment. This enables the objective, accurate, and efficient identification of off-target effects associated with TPD drugs. As a result, proteomics has become an integral aspect of TPD drug development. Conducting comprehensive and timely proteomic analyses is a key determinant of the success or failure of TPD drug development.
Workflow
1. Protein extraction from cell lines treated with different drugs.
2. Protein digestion.
3. Data Independent Acquisition (DIA) for Liquid Chromatography-Mass Spectrometry (LC-MS) Data Collection.
4. Bioinformation analysis.
5. Analysis of the Real Degradation of Proteins by TPD Drugs within Cells.
Why Choose Kinase Insight
Kinase Insight‘s targeted analysis service for TPD drugs relies on the new generation of Data Independent Acquisition (DIA) label-free quantitative proteomics technology. This cutting-edge technology has successfully analyzed the effects of PROTAC molecules such as ARV-110, along with standard product experiments (conducted through the Hela cell line). A verification experiment was performed to quantify the exogenous protein added in reduced amounts, and the results demonstrated accuracy and effectiveness.