Molecular Target Deconvolution and Identification
Capture Compound® mass spectrometry (CCMS) target identification technology facilitates the target deconvolution identification, optimization, and development of bioactive small molecules and protein biomarkers. This proprietary protein capture technology for phenotypic screening reduces time and costs during drug discovery workflows through comprehensive compound profiling and managing risk through early assessment of interactions.
CCMS technology for target deconvolution and target engagement assay data is based on:
- Trifunctional molecules – Capture Compounds®
- Chemistry know-how for tailored design
- Proprietary workflow
- No solid matrix, in solution application
- Specificity controls
- Covalent crosslinking for high sensitivity
CCMS delivers a ranked short list of specific protein interactors for any small molecule. Watch the video to learn more.
Target Deconvolution Technology
This video illustrates how this compound profiling and target deconvolution technology by Charles River deciphers protein binding patterns in an unbiased way. The test candidate becomes part of the capture compound molecule, a trifunctional molecule enabling a sorting function, reactivity function and a selectivity function.
Benefits & Applications
Compound Profiling for Phenotypic Drug Discovery
CCMS-mediated target identification (ID) provides:
- Identified targets for phenotypic compound-finding campaigns
- ID of binding site and mode of interaction
- Targets in any cellular compartment (e.g., GPCRs, ion channels, cytoplasmic signaling proteins and enzymes, nuclear proteins)
- Proteins of low abundance
- Molecular target identification for mechanism of action, adverse events, or toxicities in any tissue or species
- Novel mechanistic targets for compound re-positioning
The diagram below shows capture compounds are trifunctional molecules that identify off-target and on-target binding sites of a small molecule drug.
Chemistry Decision Making for Target Validation
Target deconvolution by CCMS profiling enables:
- Prediction of human toxicity liability
- Target deconvolution guidance of lead optimization and regulatory programs to help you choose the best development candidate
- Replacement of assay development and screening
- Avoidance of unexpected events in later development
- Data-driven decision-making for crucial milestones
Managing Risk in Drug Target Proteomics
CCMS risk-prediction offers to proteomics data for:
- Information-based target deconvolution decision making
- Cross species comparisons
- Tissue comparisons
- Toxicity predictions
- Compound-specific biomarkers
- Personalized therapeutics
- Better candidate selection
- Development path design
The Drug Discovery Workflow
CCMS can be used throughout many phases of the drug discovery workflow including target deconvolution for target identification, target engagement assays for hit-to-lead, lead optimization, and clinical development. Re-profiling of a compound is useful even when a compound has successfully become a commercially available therapeutic drug, because additional compound profiling may yield another novel target.
Target Engagement Assay Services across Discovery and Development
CCMS can deliver target engagement assay data for:
- Molecular target identification from phenotypic screens
- Drug discovery support
- Biomarkers for personalization and product rescue
- Product positioning
- Compound re-purposing
- Life cycle management support
What is Capture Compound® Mass Spectrometry (CCMS)?
CCMS is a Charles River proprietary platform for the identification and characterization of small molecule-protein interactions. This compound profiling technique is used for target deconvolution during the target identification stage of drug discovery. It is also used for target engagement assays during the hit-to-lead, lead optimization, preclinical, and clinical stages.
Can I use CCMS for measuring off-target effects of my compound?
Yes, this compound profiling technology provides target engagement assay data to enable timely assessment of off-target in vivo liabilities of a lead molecule. Additionally, Charles River has a full offering of bioinformatics software tools to provide critical data on the binding site of a small molecule on a target protein. Contact a discovery specialist to learn more.
How does Capture Compound® Mass Spectrometry work?
A “competition” experiment is the primary methodology for CCMS. Capture Compounds® are incubated with a biological sample whereby a reversible, affinity-driven interaction between the selectivity function and the target proteins occurs. For the competition sample, an excess of the free ligand is added. Subsequent photo-activation of the reactivity function causes covalent binding to the proteins and in the competition sample only, non-specific proteins are covalently captured. Isolation of the captured proteins from the matrix is achieved through sorting, and the proteins undergo proteolytic digestion. Subsequently, the proteins are analyzed by high resolution LC-MS/MS. Interrogation of the mass spectrometry data enables identification of specific binding proteins.
When should I use Capture Compound® Mass Spectrometry (CCMS)?
During drug discovery and development, assessing your lead molecule’s off-target liabilities and identifying mechanisms of toxicity early are critical to a successful path to IND. Know toxicity liabilities early by using CCMS for target deconvolution during target identification, target engagement assays during the hit-to-lead, lead optimization, preclinical and beyond.