AXXAM

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  1. Hit & Lead Discovery>

Hit-to-Lead

Independently from how the hits are identified (high-throughput screening campaigns, virtual screenings, artificial
intelligence approach, etc.), we offer solutions within the Hit-to-Lead selection process of our clients’ projects for monitoring improvement in potency and addressing selectivity, specificity and safety liabilities of the compounds as well as testing analogs in structure-activity relationships (SAR) processes.

We give value to the chemical matter!

Each of the following activities can be part of an integrated drug discovery program performed at Axxam or accessed separately, taking advantage of our extensive collection of immediately available ready-to-use assays, developing of customized assays de novo or working on assays transferred directly to us by clients.

  • Potency determination (IC50 and EC50 values) against the primary assay (target of interest)
  • Specificity profiling using orthogonal assay formats
  • Selectivity profiling against close homologues of the primary target
  • Proof of concept studies in physiologically relevant orthogonal assays and cell types
  • Mechanism of action studies (like residence time, mode of action, etc.)
  • Cardiac / CNS preliminary liability against most relevant targets
Depending on the client’s needs and on the type of activity requested, the profiling can be performed on demand or a regular basis (weekly, bi-weekly or monthly) to support hit-to-lead identification and optimization processes. The MedChem part of the Hit-to-Lead program can be performed at the client’s site, at our trusted partner Symeres or at a third provider selected by our clients. In case of regular testing, the usual turnaround time from the compound arrival at Axxam to the delivery of the results to clients is of 5 working days.

The profiling can be performed on assays designed toward a specific target (such as GPCRs, ion channels, transporters, enzymes, etc.) in cell-based and cell-free background, or to study a pathway of interest. Several readouts are available including all optical modalities (fluorescence intensity, flurorescence polarization, HTRF, luminescence, absorbance, calcium flux, membrane potential, thallium flux), patch clamp, quantitative gene expression analysis and high-content analysis.

Data analysis is performed using the best-in-class software on the market, including Genedata, Vortex (Dotmatics) and GraphPad (Dotmatics). Data export for delivery of the results can be customized to meet clients’ needs.

As part of the hit-to-lead process, a validated cardiac safety assessment panel is available including assays for the following targets: Based on automated patch clamp analysis (QPatch, Sophion)
  • hERG
  • Nav1.5
  • Kir2.1
Based on fluorescent readout (FLIPRTETRA, Molecular Devices)
  • Cav1.2

Hit-to-Lead optimization

Need to access to more services? Thanks to our strategic alliances, we offer access to chemistry, structure-based and biophysical services for a complete hit-to-lead experience.

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