Hit Validation and Assessment

Hit Validation and Assessment

Overview of Hit Validation and Assessment

At CD BioGlyco, our hit validation and assessment services focus on verifying the activity and specificity of hits identified from DNA-encoded glycan library (DEGL) screening in the context of small molecule synthesis and drug discovery. The process involves a systematic approach that ensures only the most promising compounds are progressed for further development.

Identified Glycan-related Hits Effectively

The success of glycan-related drug discovery hinges on the precise validation of potential glycan-targeting drug candidates. Our hit validation process is crucial in this domain, as it rigorously confirms the activity and specificity of identified glycan-related hits. By confirming the reproducibility of glycan interactions and eliminating candidates with undesirable properties, we significantly enhance the success rate of glycan-focused drug discovery projects. Here are some of our hit validation and assessment-related services to help your research!

The steps of hit validation and assessment. (CD BioGlyco)

Resynthesis and testing

The identified hits from the DEGL screen are resynthesized without the DNA tag to confirm that the activity observed is due to the small molecule itself and not an artifact of the DNA tag.

Structure-activity relationship (SAR) analysis

Modifications to the chemical structure of the hit compounds are made to identify which parts of the molecule are critical for activity.

Biochemical assays

These assays measure the potency, specificity, and mechanism of action of the hit compounds against the target protein.

Biophysical methods

Techniques such as X-ray crystallography or NMR spectroscopy are used to confirm the binding mode of the hit compounds.

In vitro and in vivo testing

The validated hits are tested in cellular and animal models to assess their biological activity and pharmacokinetic properties.

Applications

  • CD BioGlyco's hit validation and assessment are particularly valuable in the development of glycan-based therapeutics. The process ensures that glycan-targeting drug candidates have the desired specificity and efficacy, which is critical in addressing diseases related to glycosylation.
  • The hit validation process is extensively used in glycobiology research to identify and validate lead compounds that modulate glycan-related biological processes.
  • CD BioGlyco's hit validation is integral to the broader drug discovery pipeline, where it helps in transitioning promising hits into lead compounds suitable for preclinical and clinical development.

Advantages

  • The meticulous hit validation process ensures that only compounds with confirmed specificity and activity advance to further stages.
  • By thoroughly validating hits and eliminating those with undesirable properties early in the process, CD BioGlyco's approach significantly reduces the financial and developmental risks associated with drug discovery.
  • The rigorous validation and assessment process helps in swiftly identifying high-quality lead compounds, enabling faster progression through the drug development pipeline.

Publication

Technology: High-throughput screening (HTS), Surface plasmon resonance (SPR), Differential scanning fluorimetry (DSF), Resonance waveguide

Journal: Journal of Biomolecular Screening

Published: 2014

Results: The study investigates the application of various biophysical techniques in the validation of hits identified through HTS. The research highlights how these methods are crucial for confirming binding interactions between low-molecular-weight compounds and target proteins, specifically through label-free assays that minimize false positives. Key technologies mentioned include dynamic light scattering, turbidometry, SPR, DSF, and resonance waveguide. These techniques provide detailed insights into the binding affinities, specificity, and selectivity of the hits, ultimately aiding in the prioritization and optimization of compounds for further drug development. The study demonstrates how these biophysical methods can streamline the hit validation process, making it more efficient and reducing the likelihood of advancing ineffective compounds to later stages of drug development.

Frequently Asked Questions

  • What is the primary purpose of hit validation in drug discovery?
    • The primary purpose of hit validation is to confirm that the identified hits from screening processes, particularly those targeting glycan structures, are truly active against the intended biological targets. This step is crucial to ensure that the compounds are specific, effective, and possess desirable drug-like properties before advancing them to lead optimization and further development stages.
  • What are the key advantages of CD BioGlyco's hit validation services?
    • The key advantages include increased specificity and efficacy of drug candidates, reduced risk of investment, accelerated drug development timelines, and a higher overall success rate in drug discovery projects. These benefits are particularly pronounced in glycan-related drug development, where specificity and targeted activity are critical.

If you are interested in glycan-related drug discovery, CD BioGlyco's hit validation and assessment services are indispensable. These services rigorously confirm the activity and specificity of identified hits, ensuring that only the most promising glycan-targeting compounds move forward in the drug development pipeline. Please feel free to contact us to discover how we can support your research and development needs.

Reference

  1. Genick, C.; et al. Applications of biophysics in high-throughput screening hit validation. Journal of Biomolecular Screening. 2014, 19(5): 707-714.
For research use only. Not intended for any clinical use.
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