The Fox System:
Enabling Advances in the
Drug Discovery & Development Pipeline
Biopharmaceutical researchers are leveraging the protein decoding power of the Flash Oxidation (Fox) Protein Footprinting System throughout the drug discovery and development pipeline for biologics.
Hydroxyl Radical Protein Footprinting (HRPF), automated by the Fox System, provides valuable structural insights and contributes to understanding 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 in your stage of the pipeline.
RESEARCH & DEVELOPMENT
Target Discovery & Validation
Overall, the Fox System contributes to target discovery and validation by delivering valuable insights into the functional relevance and therapeutic potential of potential drug targets.
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.
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.
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.
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.
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.
Fox Footprinting can provide information about the nature and strength of the interactions between hit compounds and the target protein. By assessing the degree of protection or modification at specific residues, the Fox System can help evaluate the binding affinity, stoichiometry, and selectivity of the hits. This information aids in understanding the strength of the hit-target interaction and the potential for further development.
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.
Fox Technology is valuable in Structure-Activity Relationship (SAR) studies during lead optimization. By performing Fox Footprinting experiments on a series of structurally related compounds, insights are derived into the relationship between the chemical structure of the lead compounds and their impact on protein structure and dynamics. This information aids in understanding how structural modifications influence the binding affinity, selectivity, and efficacy of the lead compounds, guiding further optimization efforts.
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 the drug’s mechanism of action, assessing its specificity and safety, and optimizing its pharmacological properties before advancing to clinical trials.
Fox-based HRPF can provide 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.
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 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.
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.
Overall, Fox Footprinting contributes to clinical drug development by providing insights into the drug’s mechanism of action, patient-specific responses, off-target effects, drug-induced protein modifications, and pharmacokinetic properties. These findings aid in optimizing the drug’s efficacy, safety, and personalized therapeutic approaches in clinical settings.
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.
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.
The Fox System can help evaluate drug-induced protein modifications. By mapping oxidative modifications, Fox Footprinting can provide 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 understanding its safety profile.
MANUFACTURING TO SURVEILLANCE
The Fox System can provide valuable insights in the latter stages of the biopharmaceutical development effort including formulation, stability testing, quality control, regulatory review, and ongoing surveillance.
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.
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.
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.
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.