Hit-to-Lead Services

Independently from how the hits are identified (high-throughput screening campaigns, virtual screenings, artificial intelligence approach, etc.), Axxam offers 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.

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 off-the-shelve assays, developing of customized assays de novo or working on assays transferred directly to us by clients.

 

  • Dose-response analysis to determine potency (IC50 and EC50 values) and discriminate between orthosteric and allosteric modulators
  • 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 / GI preliminary liability against most relevant targets

Hit-to-Lead process

Axxam provides on demand and periodic compound testing activities to support hit-to-lead lead identification and optimization processes, using either target-based or phenotypic approaches.

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.

Cell-based projects

Target-based, such as:
GPCRs (Gq, Gs, Gi)
Ion Channels (ligand- and voltage-gated)
Transporters
Nuclear hormone receptors
More examples upon request

Phenotypic approaches

Cell-free projects

Broad experience on different enzymatic classes, such as:
Oxidoreductase
Transferases (such as kinases)
Hydrolases (such as Phosphodiesterases and Proteases)
Ligases
More examples upon request

Cardiac safety profiling

As part of the hit-to-lead process, a validated cardiac safety assessment panel based on automated patch clamp analysis (QPatch) is available including assays for the following targets:

  • hERG
  • Nav1.5
  • Kir2.1

Download the QPatch Validated Cell-Based Assay List for information on other assays validated using automated patch clamp readout available at Axxam for drug development purposes.

Hit-to-lead optimization

Need to access to more services? Thanks to its strategic alliances, Axxam offers access to chemistry and structure-based services for a complete hit-to-lead experience

Membrane protein expertise
Biophysical methods
Structural biology

Med Chem studies
In vivo and in vitro ADME
Customized synthesis

Fragment screening
Structural biology
Med Chem studies