Advancing the Discovery
& Development Pipeline
Biopharmaceutical researchers can leverage the protein decoding power of the Flash Oxidation (Fox) Protein Footprinting System throughout the drug discovery and development pipeline for biologics. Radical Protein Footprinting (RPF), automated by the AutoFox System, provides valuable structural insights and understanding of the interactions between the drug and the target protein. Fox Technology can characterize binding modes, evaluate structural changes, support regulatory submissions, and ensure the quality and stability of the biologic.
Discover how you can take advantage of Fox Technology to gain valuable insights into your stage of the pipeline.
Research & Development
Target Discovery & Validation
Overall, the AutoFox System contributes to target discovery and validation by delivering valuable insights into the functional relevance and therapeutic potential of potential drug targets.
Target Identification
Fox Systems can adjudicate AI models and verify screen results produced by stochastic HTS. By labeling the target both with and without the intended ligand or therapeutic, the system can reveal binding-specific signals, discriminate true positives from artifacts, quantify ligand-induced conformational changes, and validate that predicted interactions produce the expected functional and structural outcomes.
Protein Interactions
To characterize protein interactions and study complex formation, the Fox System examines the changes in protein structure and solvent accessibility in the presence of interacting partners, identifying proteins that are involved in specific protein-protein interactions. This information aids in characterizing protein networks, signaling pathways, and potential drug targets.
Target Specificity
Fox Footprinting can assist in validating the specificity of a potential drug target by subjecting protein samples to footprinting in the presence of a specific ligand or drug candidate, assessing the direct binding of the ligand to the target protein. Fox Technology can help confirm that the identified target is indeed affected by the ligand of interest.
Binding Sites
The Fox System can contribute to the mapping of ligand binding sites on a target protein. By performing Fox Footprinting experiments in the presence and absence of a ligand or drug candidate, it is possible to identify the regions of the protein that are directly affected by the binding event. This information aids in understanding the ligand-target interaction and can guide the design of ligands with improved binding affinity and specificity.
Protein Function
Fox Technology can be employed to uncover insights into the functional regions and domains of a target protein. By subjecting the protein to footprinting, it is possible to identify regions that are critical for protein function or involved in specific interactions. This information aids in understanding the functional relevance of the target protein and its potential role in disease processes.
Hit Identification & Lead Optimization
Once potential hits or lead compounds have been identified, the Fox System provides valuable insights into the molecular interactions and structural changes induced by hit compounds and lead compounds, aiding in the rational design and optimization of potential drug candidates.
Binding Sites
In the hit identification stage, Fox Technology can be used to identify the binding sites on a target protein where small molecules or ligands interact. By subjecting the protein to hydroxyl radicals in the presence and absence of potential hits or candidate compounds, footprinting can reveal regions of the protein that are directly affected by the binding event. This information aids in the identification of the specific binding site(s) of the hit compounds, providing insights into the molecular interactions between the hit and the target.
Interaction Characterization
Fox Footprinting can provide information about the nature and strength of the interactions between hit compounds and the target protein. By detecting the specific interactions between hit compounds and target residues, the Fox System can help assess the selectivity of the hits—aiding in the understanding of the specific interaction between the therapeutic and target protein.
Binding Mode
Fox Footprinting can contribute to lead optimization by assisting in determining the binding mode of the lead compounds. By subjecting the protein to Fox Footprinting in the presence of different analogs or modifications of the lead compound, footprinting can provide insights into the binding mode and conformational changes induced by structural modifications. This information helps in selecting lead compounds with optimal binding modes that maximize the desired activity and minimize unwanted interactions.
SAR Studies
Fox Technology is valuable in Structure-Activity Relationship (SAR) studies during lead optimization. By performing Fox Footprinting studies on a series of structurally related compounds, insights are derived into the relationship between lead compound chemical structure and target engagement and target response to guide further optimization efforts.
Allosteric Effects
The Fox System can help identify and map allosteric effects induced by lead compounds in the lead optimization process. By subjecting the protein to Fox Footprinting in the presence of the lead compound, footprinting can reveal conformational changes and alterations in protein structure and dynamics, both at the binding site and distal regions. This information aids in understanding the allosteric effects of the lead compounds, guiding optimization efforts to enhance the desired functional modulation.
Preclinical & Clinical Development
Preclinical Development
Fox Footprinting contributes to preclinical drug development by furthering the understanding of the drug’s mechanism of action, assessing its specificity and safety, and optimizing its pharmacological properties before advancing to clinical trials.
Target Engagement & Binding
Fox-based HRPF delivers insights into the interactions between the lead compound and the target protein in relevant physiological conditions. By subjecting the target protein to hydroxyl radicals in the presence and absence of the drug candidate, footprinting can identify and characterize the binding sites and regions of the protein that are directly affected by the drug.
Conformational Change
Fox Footprinting can provide insights into protein conformational changes by probing the solvent accessibility and conformational changes in the target protein upon drug binding. These studies provide insights into the allosteric effects and conformational rearrangements caused by the drug candidate, helping to predict the potential downstream effects of the drug on the target protein.
Off-Target Effects
Off-target effects can be studied by subjecting non-target proteins to Fox Footprinting in the presence of the drug candidate to identify unintended protein interactions or binding events. This study is helpful in assessing the specificity of the drug candidate and minimizing potential off-target effects that could impact safety and efficacy.
Protein Modifications
Fox Technology can help identify and characterize drug-induced modifications. By mapping oxidative modifications, such as oxidation of specific amino acid residues or changes in side chain accessibility, Fox Footprinting can provide insights into the drug’s impact on protein structure and stability, important data for assessing the potential toxicity, stability, and long-term effects of the drug candidate.
Clinical Development
Overall, Fox Footprinting contributes to clinical drug development by producing findings used to optimize the drug’s efficacy, safety, and personalized therapeutic approaches in clinical settings.
Patient-Specific Response
Fox Technology can also be leveraged to understand patient-specific responses to the drug candidate. By performing footprinting experiments on patient-derived samples, it is possible to analyze protein-level changes induced by the drug and identify any variations in target engagement or drug-induced modifications across individuals, helping to tailor treatments based on individual patient characteristics and responses.
Off-Target Effects
Fox Footprinting can be used to assess potential off-target effects. By subjecting non-target proteins to footprinting in the presence of the drug, it is possible to identify unintended protein interactions or binding events. This information aids in assessing the specificity of the drug candidate in a clinical context, identifying effects that may impact safety and efficacy.
Protein Modifications
The Fox System can help evaluate drug-induced protein modifications. By mapping oxidative modifications, Fox Footprinting provides insights into the drug’s impact on protein structure, stability, and potential toxicity. This information helps assess the long-term effects of the drug candidate in patients and contributes to the understanding of the safety profile.
Manufacturing to Surveillance
Market Safety Monitoring
The Fox System provides valuable insights into the latter stages of the biopharmaceutical development effort, including formulation, stability testing, quality control, regulatory review, and ongoing surveillance.
Formulation & Stability
The Fox System can be employed during formulation development to assess the impact of formulation conditions on the protein higher-order structure. By evaluating the solvent accessibility profiles under different formulation parameters, such as pH, temperature, excipients, and storage conditions, the Fox System can guide the development of stable formulations that maintain the desired protein conformation and stability.
QA/QC
The Fox System can be utilized as a quality control tool during the manufacturing process to assess batch-to-batch consistency and ensure product quality. By comparing oxidation profiles between different batches or formulations, researchers can detect any structural deviations, modifications, or aggregation tendencies that may impact the product’s safety and efficacy. Fox-based footprinting can be used to assess the stability and structural integrity of the biologic during the manufacturing process. Data generated by the Fox System can be used to ensure consistent product quality by monitoring any potential changes in protein structure or modifications that may occur during production.
Regulatory Approval
Fox-based Hydroxyl Radical Protein Footprinting can support regulatory submissions by providing structural insights into the drug-target interaction, binding sites, and conformational changes induced by the drug. Fox Footprinting data can contribute to the overall understanding of the drug’s mechanism of action and its impact on protein structure and function.
Surveillance
Fox Footprinting can be employed in post-marketing surveillance to investigate any structural changes or modifications in the biologic that may occur over time or under different storage conditions. It can contribute to monitoring the stability and integrity of the drug during its shelf life.
The Missing Piece in Your Drug Discovery & Development Workflow
The Fox System delivers high-value insights throughout the drug discovery and development pipeline, from target identification to quality control. Gaining insights into protein structure, binding interactions, formulation effects, and stability, Fox-based studies improve the understanding of drug candidates and aid in the development of safe and effective therapeutics.