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Even though Mass Spectrometry (MS) technology has been used in pharmaceutical development for decades, it was historically considered labor-intensive and low-throughput. Nevertheless, recent technological advances in MS technology and adaptations for u-HTS have paved the way for adaptation of MS label-free readout into large-scale compound screening operations. MALDI-TOF MS ‘label-free’ u-HTS readout does not rely on fluorescent labels or coupled enzymatic reactions that often result in false-positives (e.g., auto-fluorescent compounds or inhibitors/activators of secondary reaction, etc.), thereby reducing effort in hit triaging and increasing confidence in the hit list quality. This is because instead of using indirect chemical/molecular surrogates, mass of substrate and products are directly measured to assess target activity. Typically, this is achieved with inclusion of isotopically labelled internal standards for robust quantitative measurements.
Mass Spectrometry (MS) is now integrated as read-out technology into our ultra-High Throughput Screening (uHTS) system. This technology can directly track the molecule(s) of interest without the hassle of introducing labels and the risk of such labels interfering with other components in your assay. Label-free assays can reduce the number of false positives and false negatives in your screen, which will make the hit-to-lead phase of your drug discovery programme more time- and cost-effective. By combining the RapifleX™ MALDI PharmaPulse® from Bruker with the CyBio® Well Vario pipettor from Analytik Jena for automated sample spotting, we can handle 1536-well plates fully automated and screen MS-based assays up to a speed of 0.5 seconds per sample. Additionally, this system has the option for on-target washing of your samples for reduced signal-quenching and increased assay quality and robustness. Learn more about Mass Spectrometry and watch our on-demand webinar: “Could Mass Spec be the next break-through in High-Throughput Screening?
A major challenge in evaluating the hits from HTS campaigns is to select hit compounds that are worth pursuing as a chemical scaffold in a drug discovery program. The success of any HTS campaign is largely dependent on the post-screen hit-triaging phase, particularly because of undesired compound-assay interference leading to false-positive data. Such false positives could be generally categorized into technical false-positives (e.g. quenchers, auto-fluorescence, inhibitors of secondary enzymatic reactions) and hits with undesired modes-of-action (chelators, aggregators, redox, etc.). Thus, a comprehensive hit triaging cascade of assays including target engagement biophysical assays such as TSA, MST, ITC, SPR are required. However, such conventional biophysical assay technologies are either dependent on fluorescent labels and therefore minimally de-risk the identified hits or require large amounts of reagents and generally low in throughput and laborious. Affinity Selection Mass Spectrometry (AS-MS) based on MALDI-TOF is an alternative high-throughput biophysical technique offered at Pivot Park Screening Centre, which facilitates early assessment of target engagement during hit triaging without the need for extended assay development.
The benefits of Mass spectrometry. Watch our videos
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Pivot Park – Banting Building (RE2423)
Kloosterstraat 9
5349 AB Oss
The Netherlands
Pivot Park Screening Centre
Building OP
Kloosterstraat 9
5349 AB Oss
The Netherlands
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