Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads

@article{Bergsdorf2010AffinitybasedST,
  title={Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads},
  author={Christian Bergsdorf and Johannes Ottl},
  journal={Expert Opinion on Drug Discovery},
  year={2010},
  volume={5},
  pages={1095 - 1107}
}
  • C. Bergsdorf, J. Ottl
  • Published 22 October 2010
  • Biology, Medicine
  • Expert Opinion on Drug Discovery
Importance of the field: The generation of new chemical leads as a starting point for drug development is a critical step in pharmaceutical drug discovery. High-throughput screening and the attached processes have rapidly evolved over the past few years to become one of the main sources for new leads by testing large compound libraries for activity against a target of interest in biochemical in vitro tests using the recombinant protein or cell-based assays. Very recently, the traditional… Expand
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References

SHOWING 1-10 OF 77 REFERENCES
Review Article: High-Throughput Affinity-Based Technologies for Small-Molecule Drug Discovery
TLDR
In this review, their principles and applications are described and their impact on small-molecule drug discovery is evaluated and nanotechnology is predicted to generate a significant impact on the future of affinity-based technologies. Expand
Optimizing the hit-to-lead process using SPR analysis.
  • S. Loefas
  • Biology, Medicine
  • Assay and drug development technologies
  • 2004
TLDR
The latest generation of SPR biosensors integrate the hit-to-lead process and generate a greater depth of information, providing answers that cannot be addressed by traditional end-point assays, allowing users to make more informed choices on the selection of candidate molecules prior to preclinical development. Expand
SPR-based fragment screening: advantages and applications.
TLDR
Surface plasmon resonance techniques are applied to the primary screening of large libraries comprising small molecules for drug discovery, and described case studies demonstrate the successful identification of selective low molecular weight inhibitors for pharmacologically relevant drug targets through the SPR screening of fragment libraries. Expand
The Future of High-Throughput Screening
  • L. Mayr, P. Fuerst
  • Computer Science, Medicine
  • Journal of biomolecular screening
  • 2008
TLDR
The authors predict that the trend toward further miniaturization will slow down with the implementation of 384-well, 1536- well, and 384 low-volume-well plates and that, ultimately, each hit-finding strategy will be much more project related, tailor-made, and better integrated into the broader drug discovery efforts. Expand
Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency.
TLDR
The fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms and was optimized into a resorcinol lead that is now in clinical trials for the treatment of cancer. Expand
ATLAS--a high-throughput affinity-based screening technology for soluble proteins: technology application using p38 MAP kinase.
Abstract: A general affinity-based screening assay for discovery of lead compounds binding to potential protein drug targets that is based upon protein thermal unfolding and aggregation is described.Expand
Back to basics: label-free technologies for small molecule screening.
TLDR
Recent improvements in impedance- based, optical biosensor-based, automated patch clamp and mass spectrometry technologies that have enhanced their ease of use and throughput and, hence, their utility for primary screening of small- to medium-sized compound libraries are described. Expand
Screening for Ligands Using a Generic and High-Throughput Light-Scattering-Based Assay
TLDR
The authors propose potential uses in drug discovery, structural genomics, and functional genomics as a method to evaluate small-molecule interactions, identify natural cofactors that stabilize target proteins, and identify natural substrates and products for previously uncharacterized protein targets. Expand
Kinase Drug Discovery by Affinity Selection/Mass Spectrometry (ASMS): Application to DNA Damage Checkpoint Kinase Chk1
TLDR
The authors show that drug candidates with immediate value for biological preclinical evaluation can be identified directly through ultra-efficient affinity screening of kinase enzymes and random compound mixtures through mass spectrometry. Expand
Apparent activity in high-throughput screening: origins of compound-dependent assay interference.
TLDR
Considerable progress has been made to profile representative compound libraries in an effort to identify chemical classes susceptible to producing compound interference, such as compounds commonly found to inhibit the reporter enzyme firefly luciferase, and the development of practices that have the potential to significantly reduce compound interference. Expand
...
1
2
3
4
5
...