The complex path of drug discovery involves an initial screening to identify hits, the evaluation of binding kinetics and affinity, and lead characterization. However, this process is generally long, costly, and marked by a low success rate, with a tiny percentage of drug candidates under development making it through to regulatory approval. Consequently, researchers and lab managers are always looking for innovative methods to refine and accelerate this process.
Lead discovery is a primary target for streamlining drug development. Fragment-based drug design (FBDD), which detects very small molecules or fragments that bind to a specific target, has become an increasingly popular starting point in this process. Determining which compounds to progress from initial FBDD screens can be difficult due to weak affinities, low molecular weights, and solubility limitations. To overcome these challenges, sensitive biophysical techniques, like surface plasmon resonance (SPR), can be used. SPR enables fragment screens on libraries of several thousand compounds to be completed in a reasonable period of time. When combined with a continuous analyte titration method, SPR-based screening can provide higher content information, allowing for confident, rapid characterization of hits.
The accurate determination of kinetics and affinity has an ever-increasing role in identifying and isolating therapeutic molecules. As a result, any systems developed must match the high-throughput and sensitivity needs of the user, allowing assays to be performed earlier in the workflow with minimal amounts of precious samples. This enables quicker decisions on which lead candidates to promote. Some modern kinetic tools can directly provide accurate binding kinetics and affinity data from a single analyte concentration, which can increase sample throughput and kinetic data content while cutting down on costs, sample preparation time, and the risk of error from preparing multiple sample dilutions.
Advancements in sample recovery are also pivotal, allowing for the preservation of molecules with desirable characteristics for further analysis, including critical quality attribute (CQA) testing. This is especially powerful in workflows for developing biologics-based drugs. This is advantageous for processes such as cell line development, where early identification of high-productivity clones with optimal CQAs and target specificity can significantly shorten timelines, reduce sample waste, and lead to substantial cost savings.
Download this eBook to learn more about:
- Novel methods and technologies for enhancing the efficiency and accuracy of the drug discovery process
- Recent developments in fragment-based drug design, kinetic analysis, lead characterization, biologics development, and sample recovery techniques
- How to reduce the time and cost associated with bringing new therapeutics to market