High-Throughput Screening

At the core of the drug discovery process is the screening of hundreds of thousands of compounds in a high-throughput manner using in-vitro assays. Time-sensitive and cost-effective strategies are crucial for the identification of valuable hits with a specific pharmacological activity, such as those modulating a target molecule or a cellular pathway of interest.

At Axxam, we have a long history and proven experience in high-throughput screening (HTS), enabling us to support our clients during the early phases of drug discovery, from assay design to HTS campaigns, and even further during the hit-to-lead process. Our expertise enables us not only to execute an unrivaled HTS campaign, but also to develop the most suitable hit-identification strategy, ensuring a reliable compound class that can be pursued for further drug development.

We not only find the needles, but also sort the haystack!

The fundamental ingredients for a successful hit discovery program are compound libraries, assays and screening campaigns. We carry out hit-discovery programs using either compound collections available at Axxam or our clients’ preferred library, which is handled securely at our facility. Besides small molecules, we also screen chemical mixtures, natural product extracts, oligonucleotides, and antibodies.

To run an HTS campaign, clients can access our assay-development services and ready-to-go assays – taking advantage of our broad experience working with all target classes – or transfer their own validated assays to us.

The most appropriate screening strategy is selected for any screening campaign according to the specific target’s characteristics. This approach ensures the highest probability for a successful HTS with meaningful results, providing the foundation to generate innovative lead compounds.

HTS platforms & technologies

We provide access to fully automated, state-of-the-art screening platforms designed to run biochemical and cell-based assays in a minuaturized format using a variety of detection technologies such as luminescence, fluorescence (intensity, polarization, time-resolved such as HTRF or LANCE, calcium flux, membrane potential, thallium flux), and absorbance, as well as radiometric using ligand-binding, scintillation proximity assays (SPA), flashplate assays, transporter assays.

Cell-based screenings can also be performed using electrophysiological, quantitative genetic expression, and phenotypic imaging-based readouts.

Optical Readout Modalities

Radiometric Screening

Optical readouts: all major 96-, 384-, and 1536-well formats

We run automated screening campaigns with either cell-based or biochemical assays (homogeneous and non-homogeneous) in both high-throughtput screening (384 well plate) and ultra-high-throughtput screening (1536 well plate) formats:

High-throughput patch clamp

For projects targeting ion channels or electrogenic proteins, our clients can rely on high-quality patch-clamp screening run on the SyncroPatch instrument (Nanion) integrated in a fully automated robotic platform. As well as primary screening on a large compound collection, this instrumentation can be used for:

  • Clone selection
  • Compound profiling
  • Hit validation/SAR studies

Quantitative gene expression

We can run gene expression quantification analyses in a medium-throughput manner based on TaqManTM RT-qPCR assays with several advantages:

  • Any cell type or target gene
  • More “natural” conditions
  • Multiplexing – more genes can be easily investigated
  • No false-positive hits caused by readout interference
  • Toxic compound/plate effect revealed by HK analysis

Medium/high-throughput high-content screening

Studying the effect of bioactive compounds on biological pathways in a complex cellular environment requires both, a highly sensitive instrument for imaging acquisition in miniaturized format (such as the Operetta® and Opera Phenix® systems from PerkinElmer), and the experience of a skilled team capable of analyzing the huge amount of information obtained from phenotypic screening.

  • Immortalized cell lines, iPS, and primary cells
  • Low–medium throughput
  • Cell painting approach

Click here to know more about our compound collections