TPD Discovery

Targeted Protein Degraders (TPDs) comprise a class of small molecules that induce protein degradation of a specific disease-causing protein by exploiting cellular endogenous ubiquitin-proteasome and autophagy–lysosome pathway system. In recent years, various molecule classes have evolved, including PROTACs (Proteolysis-targeting Chimeras), molecular glue, CHAMP (Chaperone-mediated Protein Degradation/Degrader), LYTAC (Lysosome-targeting Chimeras), to name a few.

PROTACs and other TPDs offer a fast and reversible chemical knock-down approach to control protein function. The impact of TPDs has changed the landscape of drug innovation. TPDs are emerging as a new therapeutic method to treat diseases such as cancer, inflammation or neurodegenerative disorders caused by the aberrant expression of a pathogenic protein. While traditional drugs can target only around 20% of the proteome, this new technology could reach the remaining 80% which is currently undruggable in terms of conventional methods, such as inhibitors and agonist/antagonists.

TPD discovery technology platforms at PicoImmune laboratories covers a variety of target protein ligands. In addition, PicoImmune has established as well as improved the TPD biological screening and testing platforms throughout the pre-clinical stages.

PicoImmune is confident in providing efficient, cost-effective, and professional services to support our clients to successfully reach their drug development milestones.

Assay Platforms and Services

Assay Platforms

targeted protein degrader discovery, ALPHA screening, Alpha assay, target binding assay

Traditional Western Blot (SDS-PAGE based, Li-COR Imaging)
Quantitative Simple Western to Quantify Degradation of Any Protein
In-Cell Western to Quantify Degradation of Any Protein
AlphaLISA or HTRF Human CRBN Binding Assay
AlphaLISA or HTRF Human VHL Binding Assay
HTRF xIAP BIR3 Binding Assay
HTRF MDM2 Binding Assay
HTRF cIAP1 Binding Assay
Live Cell NanoBRET Target Engagement Intracellular E3 Ligase Assays
Live Cell NanoBRET Ubiquitination Kinetics with PROTACs and Glues
UbiQuant S ELISA and AlphaLISA assays for measuring protein ubiquitylation
IHC Analysis of Protein Degradation in Tumor Tissues
High-Throughput Flow Cytometry
RPPA (Reverse Phase Protein Array for 500 protein targets)
Cellular Thermal Shift Assay (Cetsa)
Cell Permeability Efficacy Assay (PAMPA, Caco-2, MDCK cells)

Assay Services

Identification and characterization of new, potent, and selective ligands that bind and reprogram E3 ligase substrate specificity with our ligand binding assay
Development, characterization, and validation of the warhead end of novel PROTACs
Sensitive quantitation of PROTAC-mediated degradation of targets for DC50 and Dmax values
Evaluation of the impact of target degraders on efficacy and safety-related translational biomarkers with our automatic western blot, IHC and other platforms
Characterization PROTAC selectivity across the proteome and provide a global readout on changes in protein expression using protein microarray, such as RPPA
We are able to provide off-the-shelf assays, including: CRBN, BET-VHL binding assay, VHL and CRBN ternary complex formation assay.

Example Data

targeted protein degrader assay; targeted protein degrader discovery; simple western, PROTAC

Example 1: Simple Western to quantify IKZF1/3 degradation in human lymphoma cells treated with a molecular glue compound

targeted protein degraders; targeted protein degrader discovery; in-cell western

Example 2: In-Cell Western to quantify c-MYC degradation in MV-4-11 leukemia cells treated with a PROTAC compound

targeted protein degraders; targeted protein degrader discovery; simple western; automatic western

Example 3: Simple Western to quantify TRIM24 degradation in MCF-7 human breast cancer cells treated with a PROTAC compound

targeted protein degraders; tpd discovery; ihc staining; immunohistochemistry staining

Example 4: IHC staining of protein degradation in tumor tissues from a xenograft model

targeted protein degraders; targeted protein degrader discovery; western blot, PROTAC

Example 5: Traditional western blot to examine time kinetics of GSPT1 degradation and caspase activation in cancer cells treated with a molecular glue compound

targeted protein degraders; targeted protein degrader discovery; tpd; tpd screening; simple western

Example 6: Simple Western to quantify SALL4 and PLZF degradation in induced pluripotent stem cells (iPSCs) treated with a CRBN-binding molecular glue compounds. SALL4 and PLZF are two thalidomide-dependent cereblon neo-substrates and may be related to drug-induced teratogenicity.

Targeted Protein Degrader (TPD) Discovery

Assay Platforms and Services

Assay Platforms

Assay Services

Example Data

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