SRC homology 2 (SH2) domains play a central role in mediating protein-protein interactions by recognizing and binding phosphotyrosine residues on target proteins involved in the regulation and organization of cell signaling and macromolecular complex assembly in the cell. Overexpression or mutation of proteins that contain SH2 domains can lead to dysregulation of pathways involved in inflammation, autoimmunity and oncogenesis.
Eurofins Discovery LeadHunter® services offers unique Src Homology 2 (SH2) domain binding assays to support drug discovery initiatives in the protein-protein interaction space and in targeted protein degradation. The assays cover important targets including kinases, phosphatases, phospholipases, ubiquitin-modifying E3 ligases, adaptor proteins, Signal Transducer and Activation of Transcription (STAT), guanine nucleotide exchange factors, and signal regulators that play a central role in cytokine, growth factor and oncogenic tyrosine kinase signaling.
These novel LeadHunter assays are valuable to drug discovery programs focused on identifying therapeutics that can disrupt protein-protein interactions of a given SH2 domain and evaluating ligands that can be used as a molecular handle in the design of bifunctional degraders. Allosteric targeting of selected targets through the SH2 domain also represents a useful strategy to circumvent the emergence of drug resistance at the active site.
SH2scan assay principle has been developed using our gold standard KINOMEscan™ technology to measure selective binding of lead molecules to SH2 domains. These novel and proprietary competition binding assays quantitatively measure interactions between test compounds and 102 SH2 domain-containing human targets and disease relevant mutant variants. These assays are available to suit any drug discovery program needs.
| Services | Description | Assays | Preconfigured Panel | Customizable | Testing Conditions | Standard TAT |
|---|---|---|---|---|---|---|
| SH2MAX Panel | Largest commercial SH2 domain binding panel available for drug discovery | 102 | Yes | No | 1 concentration in duplicate or 2 concentrations in singlicate | 10 business days from scheduled panel run date |
| STAT SH2scan KdELECT Panel | SH2 domain binding assay panel targeting Signal Transducer and Activation of Transcription (STAT) proteins | 10 | Yes | No | 11 concentrations in duplicate | 10 business days |
| Kinase SH2scan KdELECT Panel | SH2 domain binding assay panel targeting kinase proteins | 26 | Yes | No | 11 concentrations in duplicate | 10 business days |
| SH2scan ELECT | A flexible “a la carte” approach for customized SH2scan profiling | 102 | No | Yes | 1 or more concentrations in duplicate | 14 business days |
| SH2scan KdELECT | Follow up study tool to quantify binding affinity of compound-SH2 domain binding interactions | 102 | No | Yes | 11 concentrations in duplicate | 10 business days |
| Custom Panels | Build your own panels of SH2scan assays | 102 | No | Yes | Inquire | Inquire |
The SH2scan platform can be coupled with our existing services for an integrated approach to drug discovery. For example, this portfolio of assays can be used in parallel with our E3scan binding assay platform, to identify ligands for an E3 ligase of interest to design bifunctional protein degraders of SH2 domain-containing proteins. In addition, our cell-based and phenotypic assays can be used downstream to evaluate the functional effects of designed small molecule inhibitors or protein degraders on the expression level of a target protein of interest or on their cellular target engagement using Eurofins Discovery’s SPRINTer, InCell and BioMAP platforms. Our synthetic chemistry services can assist in crafting the right molecules for your project.
For further information, please contact StudyDirectorsServicesSanDiego@discovery.eurofinsus.com
